4,639 results match your criteria Cancer immunology immunotherapy : CII[Journal]


Natural T cell autoreactivity to melanoma antigens: clonally expanded melanoma-antigen specific CD8 + memory T cells can be detected in healthy humans.

Cancer Immunol Immunother 2019 Feb 19. Epub 2019 Feb 19.

Research and Development Department, Cellular Technology Limited (CTL), 20521 Chagrin Boulevard, Shaker Heights, Cleveland, OH, 44122-5350, USA.

We used four-color ImmunoSpot® assays, in conjunction with peptide pools that cover the sequence of tyrosinase (Tyr), melanoma-associated antigen A3 (MAGE-A3), melanocyte antigen/melanoma antigen recognized by T cells 1 (Melan-A/MART-1), glycoprotein 100 (gp100), and New York esophageal squamous cell carcinoma-1 (NY-ESO-1) to characterize the melanoma antigen (MA)-specific CD8 + cell repertoire in PBMC of 40 healthy human donors (HD). Tyr triggered interferon gamma (IFN-γ)-secreting CD8 + T cells in 25% of HD within 24 h of antigen stimulation ex vivo. MAGE-A3, Melan-A/MART-1, and gp100 also induced recall responses in 10%, 7. Read More

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http://dx.doi.org/10.1007/s00262-018-02292-7DOI Listing
February 2019

A phase I/IIa study of the mRNA-based cancer immunotherapy CV9201 in patients with stage IIIB/IV non-small cell lung cancer.

Cancer Immunol Immunother 2019 Feb 15. Epub 2019 Feb 15.

CureVac AG, Tübingen, Germany.

CV9201 is an RNActive-based cancer immunotherapy encoding five non-small cell lung cancer-antigens: New York esophageal squamous cell carcinoma-1, melanoma antigen family C1/C2, survivin, and trophoblast glycoprotein. In a phase I/IIa dose-escalation trial, 46 patients with locally advanced (n = 7) or metastatic (n = 39) NSCLC and at least stable disease after first-line treatment received five intradermal CV9201 injections (400-1600 µg of mRNA). The primary objective of the trial was to assess safety. Read More

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http://dx.doi.org/10.1007/s00262-019-02315-xDOI Listing
February 2019
1 Read

Tumor infiltrating mast cells determine oncogenic HIF-2α-conferred immune evasion in clear cell renal cell carcinoma.

Cancer Immunol Immunother 2019 Feb 13. Epub 2019 Feb 13.

Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China.

Purpose: Hypoxia-inducible factor 2α (HIF-2α) overexpression leads to activation of angiogenic pathways. However, little is known about the association between HIF-2α expression and anti-tumor immunity in clear cell renal cell carcinoma (ccRCC). We aimed to explore how HIF-2α influenced the microenvironment and the underlying mechanisms. Read More

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http://dx.doi.org/10.1007/s00262-019-02314-yDOI Listing
February 2019
1 Read

Metronomic cyclophosphamide attenuates mTOR-mediated expansion of regulatory T cells, but does not impact clinical outcome in patients with metastatic renal cell cancer treated with everolimus.

Cancer Immunol Immunother 2019 Feb 11. Epub 2019 Feb 11.

Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam University Medical Centre, VU University Medical Centre, Vrije University, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.

Introduction: Metastatic renal cell cancer (mRCC) patients have a median overall survival (mOS) of approximately 28 months. Until recently, mammalian target of rapamycin (mTOR) inhibition with everolimus was the standard second-line treatment regimen for mRCC patients, improving median progression-free survival (mPFS). Treatment with everolimus supports the expansion of immunosuppressive regulatory T cells (Tregs), which exert a negative effect on antitumor immune responses. Read More

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http://dx.doi.org/10.1007/s00262-019-02313-zDOI Listing
February 2019

Phase II clinical trial of adoptive cell therapy for patients with metastatic melanoma with autologous tumor-infiltrating lymphocytes and low-dose interleukin-2.

Cancer Immunol Immunother 2019 Feb 11. Epub 2019 Feb 11.

Tumor Immunotherapy Program, Princess Margaret Cancer Centre, Toronto, Canada.

Adoptive cell therapy using autologous tumor-infiltrating lymphocytes (TIL) has shown significant clinical benefit, but is limited by toxicities due to a requirement for post-infusion interleukin-2 (IL-2), for which high dose is standard. To assess a modified TIL protocol using lower dose IL-2, we performed a single institution phase II protocol in unresectable, metastatic melanoma. The primary endpoint was response rate. Read More

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http://dx.doi.org/10.1007/s00262-019-02307-xDOI Listing
February 2019

Imbalances in cellular immunological parameters in blood predetermine tumor onset in a natural mouse model of breast cancer.

Cancer Immunol Immunother 2019 Feb 11. Epub 2019 Feb 11.

Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, GSP-7, ul. Miklukho-Maklaya, 16/10, Moscow, 117997, Russia.

The development of new approaches to breast cancer (BC) early diagnosis is an important objective of modern oncology. Although the role of the immune system in cancer initiation process was experimentally well established, the prognostic value of cellular blood immunological parameters (CBIPs) for BC onset prediction was not demonstrated either in clinics or in mouse models. In this study, we focused on revealing informative CBIPs for mammary cancer (MC) onset prediction in the BLRB/BYRB mouse model with a high incidence of natural MC development. Read More

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http://dx.doi.org/10.1007/s00262-019-02312-0DOI Listing
February 2019

Immunotherapy with checkpoint inhibitors in non-small cell lung cancer: insights from long-term survivors.

Cancer Immunol Immunother 2019 Feb 6. Epub 2019 Feb 6.

Lung Cancer Unit, Hospital Universitari Vall d'Hebron and Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain.

Immune checkpoint inhibitors (ICIs) targeting the programmed cell death-1 (PD-1)-programmed cell death ligand-1 (PD-L1) axis have shown promising results in non-small cell lung cancer (NSCLC) patients, some of them with persistent responses to these agents that form a population of long-term survivors. Despite the variable definition of PD-L1 positivity in tumors, an association between expression and response has been reasonably consistent in advanced NSCLC. In addition, the clinical efficacy of ICIs seems to be related to the genomic landscape of the tumor in terms of mutational burden and clonal neoantigens. Read More

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http://link.springer.com/10.1007/s00262-019-02310-2
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http://dx.doi.org/10.1007/s00262-019-02310-2DOI Listing
February 2019
5 Reads

A pilot study of interferon-alpha-2b dose reduction in the adjuvant therapy of high-risk melanoma.

Cancer Immunol Immunother 2019 Feb 6. Epub 2019 Feb 6.

Comprehensive Cancer Center, The Ohio State University, Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, N924 Doan Hall 410 W. 10th Ave, Columbus, OH, 43210-1228, USA.

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http://dx.doi.org/10.1007/s00262-019-02308-wDOI Listing
February 2019

Mutations resulting in the formation of hyperactive complement convertases support cytocidal effect of anti-CD20 immunotherapeutics.

Cancer Immunol Immunother 2019 Feb 6. Epub 2019 Feb 6.

Department of Medical Biotechnology, Intercollegiate Faculty of Biotechnology, University of Gdańsk and Medical University of Gdańsk, Dębinki 1 Street, 80-211, Gdańsk, Poland.

Anti-CD20 monoclonal antibodies (mAbs) rituximab and ofatumumab are potent activators of the classical complement pathway, and have been approved for the treatment of B-cell malignancies. However, complement exhaustion and overexpression of complement inhibitors by cancer cells diminish their therapeutic potential. The strategies of targeting membrane complement inhibitors by function-blocking antibodies and the supplementation with fresh frozen plasma have been proposed to overcome tumour cell resistance. Read More

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http://dx.doi.org/10.1007/s00262-019-02304-0DOI Listing
February 2019

Early objective response to avelumab treatment is associated with improved overall survival in patients with metastatic Merkel cell carcinoma.

Cancer Immunol Immunother 2019 Feb 5. Epub 2019 Feb 5.

Merck KGaA, Darmstadt, Germany.

Background: Response rates are primary endpoints in many oncology trials; however, correlation with overall survival (OS) is not uniform across cancer types, treatments, or lines of therapy. This study explored the association between objective response (OR) and OS in patients with chemotherapy-refractory metastatic Merkel cell carcinoma who received avelumab (anti-PD-L1).

Methods: Eighty-eight patients enrolled in JAVELIN Merkel 200 (part A; NCT02155647) received i. Read More

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http://dx.doi.org/10.1007/s00262-018-02295-4DOI Listing
February 2019
2 Reads

Correction to: CD73 expression in normal and pathological human hepatobiliopancreatic tissues.

Cancer Immunol Immunother 2019 Feb 5. Epub 2019 Feb 5.

Service of Clinical Pathology, Institute of Pathology, Lausanne University Hospital, rue du Bugnon 25, 1011, Lausanne, Switzerland.

The following information must be added to the published article. Read More

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http://dx.doi.org/10.1007/s00262-019-02309-9DOI Listing
February 2019
1 Read

The effect of anti-CTLA4 treatment on peripheral and intra-tumoral T cells in patients with hepatocellular carcinoma.

Cancer Immunol Immunother 2019 Jan 28. Epub 2019 Jan 28.

Gastrointestinal Malignancies Section, Thoracic and GI Oncology Branch, Center for Cancer Research, National Cancer Institute (NCI), National Institutes of Health (NIH), Building 10, Room 3B43, Bethesda, MD, 20892, USA.

Background: Checkpoint inhibitors have recently been approved for the treatment of patients with hepatocellular carcinoma (HCC). However, biomarkers, which will help identify patients responding to therapy, are missing. We recently tested the combination of anti-CTLA4 treatment (tremelimumab) with loco-regional therapy in patients with HCC and reported a partial response rate of 26%. Read More

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http://dx.doi.org/10.1007/s00262-019-02299-8DOI Listing
January 2019
1 Read

Deciphering myeloid-derived suppressor cells: isolation and markers in humans, mice and non-human primates.

Cancer Immunol Immunother 2019 Jan 25. Epub 2019 Jan 25.

Radiotherapy and OncoImmunology Laboratory, Department of Radiation Oncology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Geert Grooteplein 28, 6500 HB, Nijmegen, The Netherlands.

In cancer, infection and inflammation, the immune system's function can be dysregulated. Instead of fighting disease, immune cells may increase pathology and suppress host-protective immune responses. Myeloid cells show high plasticity and adapt to changing conditions and pathological challenges. Read More

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http://dx.doi.org/10.1007/s00262-019-02302-2DOI Listing
January 2019
2 Reads

A potential role for peripheral natural killer cell activity induced by preoperative chemotherapy in breast cancer patients.

Cancer Immunol Immunother 2019 Jan 23. Epub 2019 Jan 23.

Department of Anatomical Pathology, Hiroshima University Hospital, 2-3, 1-Chome Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.

Tumor-infiltrating lymphocytes are an important prognostic factor after neoadjuvant chemotherapy (NAC) in patients with breast cancer. Natural killer (NK) cells play critical roles in antitumor immune surveillance. Here, we assessed the relationship between peripheral natural killer (pNK) cell activity, tumor microenvironmental factors (TMEFs), and the therapeutic efficacy of preoperative chemotherapy in patients with breast cancer. Read More

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http://dx.doi.org/10.1007/s00262-019-02305-zDOI Listing
January 2019
2 Reads

Prognostic value of tumour-infiltrating CD8+ lymphocytes in rectal cancer after neoadjuvant chemoradiation: is indoleamine-2,3-dioxygenase (IDO1) a friend or foe?

Cancer Immunol Immunother 2019 Jan 22. Epub 2019 Jan 22.

Department of General-, Visceral-, Transplant-, Vascular- and Paediatric Surgery, University Hospital of Würzburg, Oberdürrbacherstr. 6, 97080, Würzburg, Germany.

The prognostic value of the local immune phenotype in patients with colorectal cancer has been extensively studied. Neoadjuvant radiotherapy and/or chemotherapy may potentially influence these immune responses. In this study, we examined the prognostic role of indoleamine-2,3-Dioxygenase (IDO1) and infiltrating cytotoxic T lymphocytes (CD8+) in locally advanced rectal carcinomas after neoadjuvant treatment. Read More

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http://dx.doi.org/10.1007/s00262-019-02306-yDOI Listing
January 2019
1 Read

Immune checkpoint inhibitor-induced colitis as a predictor of survival in metastatic melanoma.

Cancer Immunol Immunother 2019 Jan 21. Epub 2019 Jan 21.

Department of Gastroenterology, Hepatology and Nutrition, The University of Texas, MD Anderson Cancer Center, Houston, TX, 77030, USA.

Background: Gastrointestinal (GI) immune-related adverse events (irAEs) commonly limit immune checkpoint inhibitors' (ICIs) treatment, which is very effective for metastatic melanoma. The independent impact of GI-irAEs on patients' survival is not well studied. We aimed to assess the impact of GI-irAEs on survival rates of patients with metastatic melanoma using multivariate model. Read More

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http://link.springer.com/10.1007/s00262-019-02303-1
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http://dx.doi.org/10.1007/s00262-019-02303-1DOI Listing
January 2019
8 Reads
3.941 Impact Factor

Adverse events need for hospitalization and systemic immunosuppression in very elderly patients (over 80 years) treated with ipilimumab for metastatic melanoma.

Cancer Immunol Immunother 2019 Jan 19. Epub 2019 Jan 19.

Hôpital Saint André, service de Dermatologie, University Hospital of Bordeaux, 1 rue Jean Burguet, 33000, Bordeaux, France.

Background: Checkpoint inhibitors are first-line therapies in melanoma, but safety in older adults has not yet been assessed. Ipilimumab improves survival, but immunologic-related adverse events (AEs) can be threatening, and its use in elderly people raises questions.

Aim: To assess safety in a cohort of very elderly patients treated with ipilimumab. Read More

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http://link.springer.com/10.1007/s00262-019-02298-9
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http://dx.doi.org/10.1007/s00262-019-02298-9DOI Listing
January 2019
4 Reads

Strong antigen-specific T-cell immunity induced by a recombinant human TERT measles virus vaccine and amplified by a DNA/viral vector prime boost in IFNAR/CD46 mice.

Cancer Immunol Immunother 2019 Jan 17. Epub 2019 Jan 17.

Invectys, Pépinière Paris Santé Cochin, 27, rue du Faubourg Saint Jacques, 75014, Paris, France.

Cancer immunotherapy is seeing an increasing focus on vaccination with tumor-associated antigens (TAAs). Human telomerase (hTERT) is a TAA expressed by most tumors to overcome telomere shortening. Tolerance to hTERT can be easily broken both naturally and experimentally and hTERT DNA vaccine candidates have been introduced in clinical trials. Read More

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http://dx.doi.org/10.1007/s00262-018-2272-3DOI Listing
January 2019
2 Reads

The effect of everolimus and low-dose cyclophosphamide on immune cell subsets in patients with metastatic renal cell carcinoma: results from a phase I clinical trial.

Cancer Immunol Immunother 2019 Jan 17. Epub 2019 Jan 17.

Department of Medical Oncology, Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.

For the treatment of metastatic renal cell cancer several strategies are used among which the mTOR inhibitor everolimus. As mTOR plays an important role in the immune system, e.g. Read More

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http://dx.doi.org/10.1007/s00262-018-2288-8DOI Listing
January 2019
2 Reads

STAT3 inhibition specifically in human monocytes and macrophages by CD163-targeted corosolic acid-containing liposomes.

Cancer Immunol Immunother 2019 Jan 14. Epub 2019 Jan 14.

Department of Clinical Biochemistry, Aarhus University Hospital, Palle Juul-Jensen Boulevard 99, 8200, Aarhus N, Denmark.

Tumor-associated macrophages (TAMs) are of major importance in cancer-related immune suppression, and tumor infiltration by CD163 TAMs is associated with poor outcome in most human cancers. Therefore, therapeutic strategies for reprogramming TAMs from a tumor-supporting (M2-like) phenotype towards a tumoricidal (M1-like) phenotype are of great interest. Activation of the transcription factor STAT3 within the tumor microenvironment is associated with worse prognosis, and STAT3 activation promotes the immunosuppressive phenotype of TAMs. Read More

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http://link.springer.com/10.1007/s00262-019-02301-3
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http://dx.doi.org/10.1007/s00262-019-02301-3DOI Listing
January 2019
6 Reads

Chronic retroviral infection of mice promotes tumor development, but CD137 agonist therapy restores effective tumor immune surveillance.

Cancer Immunol Immunother 2019 Jan 11. Epub 2019 Jan 11.

Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Virchowstraße 179, 45147, Essen, Germany.

T cell responses are crucial for anti-tumor immunity. In chronic viral infections, anti-tumor T cell responses can be compromised due to various immunological mechanisms, including T cell exhaustion. To study mechanisms of anti-tumor immunity during a chronic viral infection, we made use of the well-established Friend virus (FV) mouse model. Read More

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http://link.springer.com/10.1007/s00262-019-02300-4
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http://dx.doi.org/10.1007/s00262-019-02300-4DOI Listing
January 2019
5 Reads

CD73 expression in normal and pathological human hepatobiliopancreatic tissues.

Cancer Immunol Immunother 2019 Jan 4. Epub 2019 Jan 4.

Service of Clinical Pathology, Institute of Pathology, Lausanne University Hospital, rue du Bugnon 25, 1011, Lausanne, Switzerland.

Background: The tumor-expressed CD73 ectonucleotidase generates immune tolerance and promotes invasiveness via adenosine production from degradation of AMP. While anti-CD73 blockade treatment is a promising tool in cancer immunotherapy, a characterization of CD73 expression in human hepatobiliopancreatic system is lacking.

Patients And Methods: CD73 expression was investigated by immunohistochemistry in a variety of non-neoplastic and neoplastic conditions of the liver, pancreas, and biliary tract. Read More

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http://link.springer.com/10.1007/s00262-018-2290-1
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http://dx.doi.org/10.1007/s00262-018-2290-1DOI Listing
January 2019
18 Reads

Schwann cells shape the neuro-immune environs and control cancer progression.

Cancer Immunol Immunother 2019 Jan 3. Epub 2019 Jan 3.

Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.

At present, significant experimental and clinical data confirm the active involvement of the peripheral nervous system (PNS) in different phases of cancer development and progression. Most of the research effort focuses on the impact of distinct neuronal types, e.g. Read More

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http://link.springer.com/10.1007/s00262-018-02296-3
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http://dx.doi.org/10.1007/s00262-018-02296-3DOI Listing
January 2019
4 Reads

Distinct immunological properties of the two histological subtypes of adenocarcinoma of the ampulla of Vater.

Cancer Immunol Immunother 2019 Jan 2. Epub 2019 Jan 2.

Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.

Adenocarcinoma of the ampulla of Vater (AOV) is classified into intestinal type (IT) and pancreatobiliary type (PB); however, the immunological properties of these subtypes remain to be characterized. Here, we evaluated the clinical implications of PD-L1 expression and CD8 T lymphocyte density in adenocarcinomas of the AOV and their potential association with Yes-associated protein (YAP). We analyzed 123 adenocarcinoma-of-the-AOV patients who underwent surgical resection, and tumors were classified into IT or PB type. Read More

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http://dx.doi.org/10.1007/s00262-018-02293-6DOI Listing
January 2019
2 Reads

The route of administration dictates the immunogenicity of peptide-based cancer vaccines in mice.

Cancer Immunol Immunother 2019 Jan 2. Epub 2019 Jan 2.

Cancer Immunology, Inflammation and Tolerance Program, Georgia Cancer Center, Augusta University, 1410 Laney Walker Blvd., CN-4142, Augusta, GA, 30912, USA.

Vaccines consisting of synthetic peptides representing cytotoxic T-lymphocyte (CTL) epitopes have long been considered as a simple and cost-effective approach to treat cancer. However, the efficacy of these vaccines in the clinic in patients with measurable disease remains questionable. We believe that the poor performance of peptide vaccines is due to their inability to generate sufficiently large CTL responses that are required to have a positive impact against established tumors. Read More

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http://link.springer.com/10.1007/s00262-018-02294-5
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http://dx.doi.org/10.1007/s00262-018-02294-5DOI Listing
January 2019
2 Reads

Randomized-controlled phase II trial of salvage chemotherapy after immunization with a TP53-transfected dendritic cell-based vaccine (Ad.p53-DC) in patients with recurrent small cell lung cancer.

Cancer Immunol Immunother 2018 Dec 27. Epub 2018 Dec 27.

Department of Thoracic Oncology, H. Lee Moffitt Cancer Center and Research Institute, 12902, Magnolia Drive, FOB1, Tampa, FL, 33612, USA.

Small cell lung cancer TP53 mutations lead to expression of tumor antigens that elicits specific cytotoxic T-cell immune responses. In this phase II study, dendritic cells transfected with wild-type TP53 (vaccine) were administered to patients with extensive-stage small cell lung cancer after chemotherapy. Patients were randomized 1:1:1 to arm A (observation), arm B (vaccine alone), or arm C (vaccine plus all-trans-retinoic acid). Read More

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http://dx.doi.org/10.1007/s00262-018-2287-9DOI Listing
December 2018
1 Read

MDSCs in infectious diseases: regulation, roles, and readjustment.

Cancer Immunol Immunother 2018 Dec 19. Epub 2018 Dec 19.

Nuclear Receptor Group, Department of Cell Biology, Physiology and Immunology, School of Biology, University of Barcelona, Av. Diagonal, 643, 3rd floor, 08028, Barcelona, Spain.

Many pathogens, ranging from viruses to multicellular parasites, promote expansion of MDSCs, which are myeloid cells that exhibit immunosuppressive features. The roles of MDSCs in infection depend on the class and virulence mechanisms of the pathogen, the stage of the disease, and the pathology associated with the infection. This work compiles evidence supported by functional assays on the roles of different subsets of MDSCs in acute and chronic infections, including pathogen-associated malignancies, and discusses strategies to modulate MDSC dynamics to benefit the host. Read More

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http://dx.doi.org/10.1007/s00262-018-2277-yDOI Listing
December 2018
2 Reads

Immune cell infiltration as a biomarker for the diagnosis and prognosis of stage I-III colon cancer.

Cancer Immunol Immunother 2018 Dec 19. Epub 2018 Dec 19.

Department of Oncology, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou, 510515, People's Republic of China.

Tumour-infiltrating immune cells are a source of important prognostic information for patients with resectable colon cancer. We developed a novel immune model based on systematic assessments of the immune landscape inferred from bulk tumor transcriptomes of stage I-III colon cancer patients. The "Cell type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT)" algorithm was used to estimate the fraction of 22 immune cell types from six microarray public datasets. Read More

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http://link.springer.com/10.1007/s00262-018-2289-7
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http://dx.doi.org/10.1007/s00262-018-2289-7DOI Listing
December 2018
10 Reads

A secreted PD-L1 splice variant that covalently dimerizes and mediates immunosuppression.

Cancer Immunol Immunother 2018 Dec 18. Epub 2018 Dec 18.

Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, 450 Brookline Ave., Boston, MA, 02215, USA.

Targeting immune checkpoint pathways, such as programmed death ligand-1 (PD-L1, also known as CD274 or B7-H1) or its receptor programmed cell death-1 (PD-1) has shown improved survival for patients with numerous types of cancers, not limited to lung cancer, melanoma, renal cell carcinoma, and Hodgkin lymphoma. PD-L1 is a co-inhibitory molecule whose expression on the surface of tumor cells is associated with worse prognosis in many tumors. Here we describe a splice variant (secPD-L1) that does not splice into the transmembrane domain, but instead produces a secreted form of PD-L1 that has a unique 18 amino acid tail containing a cysteine that allows it to homodimerize and more effectively inhibit lymphocyte function than monomeric soluble PD-L1. Read More

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http://link.springer.com/10.1007/s00262-018-2282-1
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http://dx.doi.org/10.1007/s00262-018-2282-1DOI Listing
December 2018
8 Reads

Identification and characterization of an alternative cancer-derived PD-L1 splice variant.

Cancer Immunol Immunother 2018 Dec 18. Epub 2018 Dec 18.

Department of Pathology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX, 75390, USA.

Therapeutic blockade of the PD-1/PD-L1 axis is recognized as an effective treatment for numerous cancer types. However, only a subset of patients respond to this treatment, warranting a greater understanding of the biological mechanisms driving immune evasion via PD-1/PD-L1 signaling and other T-cell suppressive pathways. We previously identified a head and neck squamous cell carcinoma with human papillomavirus integration in the PD-L1 locus upstream of the transmembrane domain-encoding region, suggesting expression of a truncated form of PD-L1 (Parfenov et al. Read More

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http://link.springer.com/10.1007/s00262-018-2284-z
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http://dx.doi.org/10.1007/s00262-018-2284-zDOI Listing
December 2018
14 Reads

Addressing current challenges and future directions in immuno-oncology: expert perspectives from the 2017 NIBIT Foundation Think Tank, Siena, Italy.

Cancer Immunol Immunother 2019 Jan 18;68(1):1-9. Epub 2018 Dec 18.

Parker Institute for Cancer Immunotherapy, 1 Letterman Drive, San Francisco, CA, 94129, USA.

A collaborative think tank involving panellists from immuno-oncology networks, clinical/translational investigators and the pharmaceutical industry was held in Siena, Italy, in October 2017 to discuss the evolving immune-oncology landscape, identify selected key challenges, and provide a perspective on the next steps required in the translation of current research and knowledge to clinical reality. While there is a trend of combining new agents (e.g. Read More

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http://dx.doi.org/10.1007/s00262-018-2285-yDOI Listing
January 2019
3 Reads

The Italian Network for Tumor Bio-Immunotherapy (NIBIT) Foundation: ongoing and prospective activities in immuno-oncology.

Cancer Immunol Immunother 2019 Jan 18;68(1):143-150. Epub 2018 Dec 18.

Center for Immuno-Oncology, Medical Oncology and Immunotherapy, University Hospital of Siena, Istituto Toscano Tumori, Viale Mario Bracci, 16, 53100, Siena, Italy.

The ongoing revolution in cancer immunotherapy stems from the knowledge that distinct immune-checkpoints regulate the physiological crosstalk between and among immune cells by delivering inhibitory or activating signals. These notions, and the availability of mAb directed to diverse immune-checkpoint molecules, have led to a significant clinical improvement in cancer treatment. In this scenario, further achievements are undoubtedly to be expected from the contribution of novel, proof-of-principle clinical trials designed to explore the therapeutic efficacy of new immunotherapy-based combinations and treatment sequences. Read More

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http://link.springer.com/10.1007/s00262-018-2286-x
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http://dx.doi.org/10.1007/s00262-018-2286-xDOI Listing
January 2019
10 Reads

Ex vivo conditioning with IL-12 protects tumor-infiltrating CD8 T cells from negative regulation by local IFN-γ.

Cancer Immunol Immunother 2018 Dec 14. Epub 2018 Dec 14.

Department of Inflammation and Immunity, Cleveland Clinic, Lerner Research Institute, 9500 Euclid Avenue NE40, Cleveland, OH, 44195, USA.

Optimal ex vivo expansion protocols for adoptive cell therapy (ACT) must yield T cells able to effectively home to tumors and survive the inhospitable conditions of the tumor microenvironment (TME), while simultaneously exerting persistent anti-tumor effector functions. Our previous work has shown that ex vivo activation in the presence of IL-12 can induce optimal expansion of murine CD8 T cells, thus resulting in significant tumor regression after ACT mostly via sustained secretion of IFN-γ. In this report, we further elucidate the mechanism of this potency, showing that IL-12 additionally counteracts the negative regulatory effects of autocrine IFN-γ. Read More

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http://dx.doi.org/10.1007/s00262-018-2280-3DOI Listing
December 2018
11 Reads

Enhanced anti-tumor efficacy of checkpoint inhibitors in combination with the histone deacetylase inhibitor Belinostat in a murine hepatocellular carcinoma model.

Cancer Immunol Immunother 2018 Dec 13. Epub 2018 Dec 13.

Center for Applied Medical Research (CIMA), Program of Immunology and Immunotherapy, University of Navarra, Pío XII 55, 31008, Pamplona, Spain.

Immune checkpoint inhibitors are currently tested in different combinations in patients with advanced hepatocellular carcinoma (HCC). Nivolumab, an anti-PD-1 agent, has gained approval in the second-line setting in the USA. Epigenetic drugs have immune-mediated antitumor effects that may improve the activity of immunotherapy agents. Read More

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http://link.springer.com/10.1007/s00262-018-2283-0
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http://dx.doi.org/10.1007/s00262-018-2283-0DOI Listing
December 2018
11 Reads

CRISPR/Cas9-mediated PD-1 disruption enhances human mesothelin-targeted CAR T cell effector functions.

Cancer Immunol Immunother 2018 Dec 6. Epub 2018 Dec 6.

Sheng Yushou Center of Cell Biology and Immunology, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, 800 Dongchuan Road, Minghang, Shanghai, 200240, China.

The interaction between programmed cell death protein 1 (PD-1) on activated T cells and its ligands on a target tumour may limit the capacity of chimeric antigen receptor (CAR) T cells to eradicate solid tumours. PD-1 blockade could potentially enhance CAR T cell function. Here, we show that mesothelin is overexpressed in human triple-negative breast cancer cells and can be targeted by CAR T cells. Read More

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http://dx.doi.org/10.1007/s00262-018-2281-2DOI Listing
December 2018
1 Read

The correlation and prognostic value of serum levels of soluble programmed death protein 1 (sPD-1) and soluble programmed death-ligand 1 (sPD-L1) in patients with hepatocellular carcinoma.

Cancer Immunol Immunother 2018 Dec 1. Epub 2018 Dec 1.

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, People's Republic of China.

Background: Blocking the programmed death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) pathway in hepatocellular carcinoma (HCC) is a very promising approach in immunotherapy. However, the correlation and prognostic values of serum soluble PD-1 and PD-L1 (sPD-1/sPD-L1) have not been explored conjointly in HCC patients.

Methods: This study retrospectively included 120 HCC patients receiving radical resection. Read More

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http://link.springer.com/10.1007/s00262-018-2271-4
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http://dx.doi.org/10.1007/s00262-018-2271-4DOI Listing
December 2018
19 Reads
3.941 Impact Factor

Tumor-infiltrating immune cell subpopulations and programmed death ligand 1 (PD-L1) expression associated with clinicopathological and prognostic parameters in ependymoma.

Cancer Immunol Immunother 2019 Feb 27;68(2):305-318. Epub 2018 Nov 27.

Department of Pathology, Asan Medical Center, Seoul, South Korea.

Ependymomas are biologically and clinically heterogeneous tumors of the central nervous system that have variable clinical outcomes. The status of the tumor immune microenvironment in ependymoma remains unclear. Immune cell subsets and programmed death ligand 1 (PD-L1) expression were measured in 178 classical ependymoma cases by immunohistochemistry using monoclonal antibodies that recognized tumor-infiltrating lymphocyte subsets (TILs; CD3, CD4, CD8, FOXP3, and CD20), tumor-associated macrophages (TAMs; CD68, CD163, AIF1), indoleamine 2,3-dioxygenase (IDO)+ cells and PD-L1-expressing tumor cells. Read More

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http://link.springer.com/10.1007/s00262-018-2278-x
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http://dx.doi.org/10.1007/s00262-018-2278-xDOI Listing
February 2019
4 Reads

Can benign lymphoid tissue changes in F-FDG PET/CT predict response to immunotherapy in metastatic melanoma?

Cancer Immunol Immunother 2019 Feb 26;68(2):297-303. Epub 2018 Nov 26.

Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69210, Heidelberg, Germany.

Background: An association between immune-related adverse events (irAEs) caused by immunotherapeutic agents and the clinical benefit of immunotherapy has been suggested. We retrospectively evaluated by means of F-FDG PET/CT lymphoid tissue changes in the mediastinal/hilar lymph nodes and the spleen in response to ipilimumab administration in metastatic melanoma.

Methods: A total of 41 patients with unresectable metastatic melanoma underwent F-FDG PET/CT before the start of ipilimumab (baseline PET/CT), after two cycles (interim PET/CT) and at the end of treatment (late PET/CT). Read More

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http://dx.doi.org/10.1007/s00262-018-2279-9DOI Listing
February 2019
1 Read

An alphavirus-based therapeutic cancer vaccine: from design to clinical trial.

Cancer Immunol Immunother 2018 Nov 21. Epub 2018 Nov 21.

Department of Medical Microbiology, Tumor Virology and Cancer Immunotherapy, University of Groningen, University Medical Center Groningen, HPC EB88, PO Box 30.001, 9700RB, Groningen, The Netherlands.

Cancer immunotherapy has greatly advanced in recent years. Most immunotherapeutic strategies are based on the use of immune checkpoint blockade to unleash antitumor immune responses or on the induction or adoptive transfer of immune effector cells. We aim to develop therapeutic vaccines based on recombinant Semliki Forest virus vectors to induce tumor-specific effector immune cells. Read More

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http://dx.doi.org/10.1007/s00262-018-2276-zDOI Listing
November 2018
16 Reads

Upregulation of tumor PD-L1 by neoadjuvant chemoradiotherapy (neoCRT) confers improved survival in patients with lymph node metastasis of locally advanced rectal cancers.

Cancer Immunol Immunother 2019 Feb 17;68(2):283-296. Epub 2018 Nov 17.

Cancer Center, China Medical University Hospital, China Medical University, 9F, Rehab Building, No. 2 Rude Rd, Taichung, 40402, Taiwan.

The expression of programmed cell death 1 ligand 1 (PD-L1) and interferon-γ (IFN-γ) is of great interest for the development of chemoradiotherapy and immune checkpoint inhibitor treatments. Patients with nodal metastasis (pN+) tend to have a poor prognosis, even after neoadjuvant chemoradiotherapy (neoCRT) and surgical treatment. In this study, we examined the roles of tumor PD-L1 and IFN-γ before and after neoCRT in locally advanced rectal cancer (LARC) patients. Read More

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http://link.springer.com/10.1007/s00262-018-2275-0
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http://dx.doi.org/10.1007/s00262-018-2275-0DOI Listing
February 2019
9 Reads
3.941 Impact Factor

A phase I clinical study of a cocktail vaccine of Wilms' tumor 1 (WT1) HLA class I and II peptides for recurrent malignant glioma.

Cancer Immunol Immunother 2019 Feb 14;68(2):331-340. Epub 2018 Nov 14.

Department of Cancer Immunology, Osaka University Graduate School of Medicine, Osaka, Japan.

Purpose: The safety and clinical efficacy of WT1 human leukocyte antigen (HLA) class I peptide vaccine have been established, but the safety of a cocktail vaccine of WT1 HLA class I and II peptides has not. To verify its safety, we performed a phase I clinical trial for patients with recurrent malignant gliomas and assessed the immunological responses and survival data.

Patients And Methods: Fourteen HLA-A*24:02-positive patients with recurrent malignant glioma (2 with grade 3, 12 with grade 4) were enrolled. Read More

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http://dx.doi.org/10.1007/s00262-018-2274-1DOI Listing
February 2019
2 Reads

Targeting the polarization of tumor-associated macrophages and modulating mir-155 expression might be a new approach to treat diffuse large B-cell lymphoma of the elderly.

Cancer Immunol Immunother 2019 Feb 14;68(2):269-282. Epub 2018 Nov 14.

Department of Clinical and Experimental Oncology, Universidade Federal de São Paulo, Rua Diogo de Faria, 824, 5° andar, Hemocentro, CEP 04037-002, Sao Paulo, Brazil.

Aging immune deterioration and Epstein-Barr (EBV) intrinsic mechanisms play an essential role in EBV-positive diffuse large B-cell lymphoma (DLBCL) of the elderly (EBV + DLBCLe) pathogenesis, through the expression of viral proteins, interaction with host molecules and epigenetic regulation, such as miR-155, required for induction of M1 phenotype of macrophages. This study aims to evaluate the relationship between macrophage polarization pattern in the tumor microenvironment and relative expression of miR-155 in EBV + DLBCLe and EBV-negative DLBCL patients. We studied 28 EBV + DLBCLe and 65 EBV-negative DLBCL patients. Read More

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http://dx.doi.org/10.1007/s00262-018-2273-2DOI Listing
February 2019
6 Reads

Phase 1 study of everolimus and low-dose oral cyclophosphamide in patients with metastatic renal cell carcinoma.

Cancer Immunol Immunother 2019 Feb 9;68(2):319-329. Epub 2018 Nov 9.

Department of Medical Oncology, VU University Medical Center, Cancer Center Amsterdam, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.

mTOR inhibitors are frequently used in the treatment of metastatic renal cell cancer (mRCC). mTOR regulates cell growth, proliferation, angiogenesis, and survival, and additionally plays an important role in immune regulation. Since mTOR inhibitors were shown to benefit immunosuppressive regulatory T-cell (Treg) expansion, this might suppress antitumor immune responses. Read More

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http://dx.doi.org/10.1007/s00262-018-2248-3DOI Listing
February 2019
8 Reads

The nature of the human T cell response to the cancer antigen 5T4 is determined by the balance of regulatory and inflammatory T cells of the same antigen-specificity: implications for vaccine design.

Cancer Immunol Immunother 2019 Feb 7;68(2):247-256. Epub 2018 Nov 7.

Division of Infection and Immunity, Henry Wellcome Building, Cardiff University, Health Park, Cardiff, CF14 4XN, UK.

The oncofoetal antigen 5T4 is a promising T cell target in the context of colorectal cancer, as demonstrated by a recent clinical study where 5T4-specific T cell responses, induced by vaccination or cyclophosphamide, were associated with a significantly prolonged survival of patients with metastatic disease. Whilst Th1-type (IFN-γ) responses specific to 5T4, and other oncofoetal antigens, are often readily detectable in early stage CRC patients and healthy donors, their activity is suppressed as the cancer progresses by CD4CD25Foxp3 regulatory T cells (Treg) which contribute to the immunosuppressive environment conducive to tumour growth. This study mapped the fine specificity of Th1 and Treg cell responses to the 5T4 protein. Read More

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http://link.springer.com/10.1007/s00262-018-2266-1
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http://dx.doi.org/10.1007/s00262-018-2266-1DOI Listing
February 2019
13 Reads

Apoptosis of tumor-infiltrating T lymphocytes: a new immune checkpoint mechanism.

Cancer Immunol Immunother 2018 Nov 7. Epub 2018 Nov 7.

Ludwig Institute for Cancer Research, 1200, Brussels, Belgium.

Immunotherapy based on checkpoint inhibitors is providing substantial clinical benefit, but only to a minority of cancer patients. The current priority is to understand why the majority of patients fail to respond. Besides T-cell dysfunction, T-cell apoptosis was reported in several recent studies as a relevant mechanism of tumoral immune resistance. Read More

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http://link.springer.com/10.1007/s00262-018-2269-y
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http://dx.doi.org/10.1007/s00262-018-2269-yDOI Listing
November 2018
10 Reads

Hyperresponsiveness to interferon gamma exposure as a response mechanism to anti-PD-1 therapy in microsatellite instability colorectal cancer.

Cancer Immunol Immunother 2019 Feb 7;68(2):257-268. Epub 2018 Nov 7.

The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital, Yunnan Cancer Center, No. 519 Kun Zhou Road, Xishan District, Kunming, 650118, Yunnan, People's Republic of China.

Colorectal cancer (CRC) with high-level microsatellite instability (MSI-H) tends to be associated with a better response to programmed death receptor-1 (PD-1) blockade than does microsatellite stable CRC. However, emerging evidence makes the use of programmed death ligand-1 (PD-L1) as a biomarker problematic. Here, we sought to characterize the interactions between PD-L1 expression and the response to PD-1 blockade therapy in BALB/c mice with a subcutaneous tumor challenge. Read More

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http://link.springer.com/10.1007/s00262-018-2270-5
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http://dx.doi.org/10.1007/s00262-018-2270-5DOI Listing
February 2019
10 Reads

Targeting CTCFL/BORIS for the immunotherapy of cancer.

Authors:
Dmitri Loukinov

Cancer Immunol Immunother 2018 Dec 2;67(12):1955-1965. Epub 2018 Nov 2.

Molecular Pathology Section, Laboratory of Immunogenetics, NIAID/NIH, Twinbrook 1, Room 1329, 5640 Fishers Lane, Rockville, MD, 20852, USA.

Cancer vaccines have great potential in the fight against metastatic malignancies. Current anti-tumor immunotherapy is hindered by existing tolerance to tumor-associated antigens (TAA) and tumor escape using various mechanisms, highlighting the need for improved targets for immunotherapy. The cancer-testis antigen CTCFL/BORIS was discovered 16 years ago and possesses all features necessary for an ideal TAA. Read More

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http://dx.doi.org/10.1007/s00262-018-2251-8DOI Listing
December 2018
10 Reads

Development of CDX-1140, an agonist CD40 antibody for cancer immunotherapy.

Cancer Immunol Immunother 2019 Feb 31;68(2):233-245. Epub 2018 Oct 31.

Celldex Therapeutics, Inc, 53 Frontage Road, Suite 220, Hampton, NJ, 08827, USA.

Limitations of immunotherapy include poorly functioning events early in the immune response cycle, such as efficient antigen presentation and T cell priming. CD40 signaling in dendritic cells leads to upregulation of cell surface costimulatory and MHC molecules and the generation of cytokines, which promotes effective priming of CD8 effector T cells while minimizing T cell anergy and the generation of regulatory T cells. This naturally occurs through interaction with CD40 ligand (CD40L) expressed on CD4 T-helper cells. Read More

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http://link.springer.com/10.1007/s00262-018-2267-0
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http://dx.doi.org/10.1007/s00262-018-2267-0DOI Listing
February 2019
15 Reads

Analysis of tumor-infiltrating CD103 resident memory T-cell content in recurrent laryngeal squamous cell carcinoma.

Cancer Immunol Immunother 2019 Feb 25;68(2):213-220. Epub 2018 Oct 25.

Department of Otolaryngology - Head and Neck Surgery, University of Michigan, 1150 E. Medical Center Dr., 9301B MSRB3, Ann Arbor, 48109-0602, MI, USA.

Background: Recurrent laryngeal squamous cell carcinomas (LSCCs) are associated with poor outcomes, without reliable biomarkers to identify patients who may benefit from adjuvant therapies. Given the emergence of tumor-infiltrating lymphocytes (TIL) as a biomarker in head and neck squamous cell carcinoma, we generated predictive models to understand the utility of CD4, CD8 and/or CD103 TIL status in patients with advanced LSCC.

Methods: Tissue microarrays were constructed from salvage laryngectomy specimens of 183 patients with recurrent/persistent LSCC and independently stained for CD4, CD8, and CD103 TIL content. Read More

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http://link.springer.com/10.1007/s00262-018-2256-3
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http://dx.doi.org/10.1007/s00262-018-2256-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6375747PMC
February 2019
23 Reads

Inhibitory functions of PD-L1 and PD-L2 in the regulation of anti-tumor immunity in murine tumor microenvironment.

Cancer Immunol Immunother 2019 Feb 24;68(2):201-211. Epub 2018 Oct 24.

Department of Immunology, Graduate School of Medicine, Yamaguchi University, 1-1-1 Minami Kogushi, Ube, Yamaguchi, 755-8505, Japan.

Although a role of PD-L1 in the suppression of anti-tumor immunity and its value as a predictive biomarker has been suggested by various preclinical and clinical studies, the precise mechanisms how PD-L1 and PD-L2, another ligand of PD-1, regulate anti-tumor immunity in the tumor microenvironment are yet to be fully explored. Here, we address this issue using PD-L1-deficient tumor cells, PD-L1-knockout (KO) mice, anti-PD-L1 monoclonal antibody (mAb), and anti-PD-L2 mAb. Firstly, PD-L1-deficient or competent tumor cells were inoculated into wild-type or PD-L1-KO mice. Read More

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http://link.springer.com/10.1007/s00262-018-2263-4
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http://dx.doi.org/10.1007/s00262-018-2263-4DOI Listing
February 2019
18 Reads