4,970 results match your criteria Cancer Immunology Immunotherapy[Journal]


Tumour microenvironment (TME) characterization identified prognosis and immunotherapy response in muscle-invasive bladder cancer (MIBC).

Cancer Immunol Immunother 2020 Jul 2. Epub 2020 Jul 2.

Department of Urology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China.

Tumour microenvironment (TME), which consists of widely diverse immune and stromal cells and the factors that they secrete, cultivates a chronic inflammatory, immunosuppressive, and pro-angiogenic intratumoural atmosphere, which has been reported to correlate with patient outcomes and treatment efficacy. In this study, we characterized TME pattern through the "Estimation of STromal and Immune cells in MAlignant Tumours using Expression data" (ESTIMATE) algorithm and build a TME-related signature (TMERS), which is serving as an independent prognostic factor in MIBC. Moreover, we found that the TMERS was highly positive correlated with immune infiltration, the expression of immune checkpoints and high malignancy molecular subtypes such as basal, infiltrated and basal/SCC-like. Read More

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http://dx.doi.org/10.1007/s00262-020-02649-xDOI Listing

Characterizing caspase-1 involvement during esophageal disease progression.

Cancer Immunol Immunother 2020 Jul 1. Epub 2020 Jul 1.

School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland.

Barrett's esophagus (BE) is an inflammatory condition and a neoplastic precursor to esophageal adenocarcinoma (EAC). Inflammasome signaling, which contributes to acute and chronic inflammation, results in caspase-1 activation leading to the secretion of IL-1β and IL-18, and inflammatory cell death (pyroptosis). This study aimed to characterize caspase-1 expression, and its functional importance, during disease progression to BE and EAC. Read More

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http://dx.doi.org/10.1007/s00262-020-02650-4DOI Listing

Induction of systemic immune responses and reversion of immunosuppression in the tumor microenvironment by a therapeutic vaccine for cervical cancer.

Cancer Immunol Immunother 2020 Jul 1. Epub 2020 Jul 1.

Department of Microbiology and Parasitology, College of Basic Medical Science, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, 110122, China.

Cervical cancer is the most common malignant tumor of the genital tract in females worldwide. Persistent human papillomavirus (HPV) infection is closely associated with the occurrence of cervical cancer. No licensed therapeutic HPV vaccines for cervical cancer are currently available. Read More

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http://dx.doi.org/10.1007/s00262-020-02651-3DOI Listing

Histopathological growth patterns correlate with the immunoscore in colorectal cancer liver metastasis patients after hepatectomy.

Cancer Immunol Immunother 2020 Jun 29. Epub 2020 Jun 29.

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

Various scoring systems have been proposed to predict the postoperative prognosis of colorectal liver metastasis (CRLM), including the clinical risk score (CRS), the immunoscore and so on. Recently, histopathological growth patterns (HGPs) have been recognized. However, the correlation between HGPs and the immunoscore, and their prognostic values in patients with CRLM after liver resection remain undetermined. Read More

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http://dx.doi.org/10.1007/s00262-020-02632-6DOI Listing

Multi-antigen DNA vaccine delivered by polyethylenimine and Salmonella enterica in neuroblastoma mouse model.

Cancer Immunol Immunother 2020 Jun 27. Epub 2020 Jun 27.

Belarusian Research Center for Pediatric Oncology, Hematology and Immunology, v. Borovlyani, Minsk, 220053, Belarus.

Neuroblastoma is an example of a difficult-to-treat tumor with high incidence of relapse. DNA vaccination could be applied as a relapse prophylactic option for patients with high-risk neuroblastoma. Its efficacy depends directly on a target antigen of choice and a delivery method. Read More

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http://dx.doi.org/10.1007/s00262-020-02652-2DOI Listing

A randomized controlled phase II clinical trial on mRNA electroporated autologous monocyte-derived dendritic cells (TriMixDC-MEL) as adjuvant treatment for stage III/IV melanoma patients who are disease-free following the resection of macrometastases.

Cancer Immunol Immunother 2020 Jun 26. Epub 2020 Jun 26.

Department of Medical Oncology, Universitair Ziekenhuis Brussel (UZ Brussel), Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090, Brussels, Belgium.

Background: Autologous monocyte-derived mRNA co-electroporated dendritic cells with mRNA encoding CD40 ligand (CD40L), CD70 and a constitutively activated TLR4 (caTLR4) (referred to as TriMixDC-MEL) have anti-tumor activity in advanced melanoma patients. We investigated the safety and activity of adjuvant TriMixDC-MEL in stage III/IV melanoma patients.

Materials And Methods: Forty-one patients were randomly assigned to treatment with TriMixDC-MEL (n = 21) and standard follow-up (n = 20). Read More

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http://dx.doi.org/10.1007/s00262-020-02618-4DOI Listing

Dynamics of peripheral T cell clones during PD-1 blockade in non-small cell lung cancer.

Cancer Immunol Immunother 2020 Jun 26. Epub 2020 Jun 26.

Beijing Advanced Innovation Center for Genomics, School of Life Sciences, BIOPIC, Peking University, Beijing, 100871, China.

Understanding of the functional states and clonal dynamics of T cells after immune checkpoint blockade (ICB) is valuable for improving these therapeutic strategies. Here we performed Smart-seq2 single-cell RNA sequencing (scRNA-seq) analysis on 3,110 peripheral T cells of non-small cell lung cancer (NSCLC) patients before and after the initiation of programmed cell death protein 1 (PD-1) blockade. We identified individual peripheral T cell clones based on the full-length T cell receptor (TCR) sequences and monitored their dynamics during immunotherapy. Read More

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http://dx.doi.org/10.1007/s00262-020-02642-4DOI Listing

Impact of corticosteroids on allograft protection in renal transplant patients receiving anti-PD-1 immunotherapy.

Cancer Immunol Immunother 2020 Jun 25. Epub 2020 Jun 25.

Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

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http://dx.doi.org/10.1007/s00262-020-02644-2DOI Listing

TIM-3 blockade combined with bispecific antibody MT110 enhances the anti-tumor effect of γδ T cells.

Cancer Immunol Immunother 2020 Jun 25. Epub 2020 Jun 25.

Department of Biochemistry and Molecular Biology, School of Basic Medicine, Qingdao University, Qingdao, 266021, China.

As ideal cells that can be used for adoptive cell therapy, γδ T cells are a group of homogeneous cells with high proliferative and tumor killing ability. However, γδ T cells are apt to apoptosis and show decreased cytotoxicity under persistent stimulation in vitro and cannot aggregate at tumor sites efficiently in vivo, both of which are two main obstacles to tumor adoptive immunotherapy. In this study, we found that the immune checkpoint T-cell immunoglobulin domain and mucin domain 3 (TIM-3) were up-regulated significantly on γδ T cells during their ex vivo expansion and this up-regulation contributed to the dysfunction of γδ T cells. Read More

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http://dx.doi.org/10.1007/s00262-020-02638-0DOI Listing

Increased IL-10+CD206+CD14+M2-like macrophages in alveolar lavage fluid of patients with small cell lung cancer.

Cancer Immunol Immunother 2020 Jun 24. Epub 2020 Jun 24.

Genetic Diagnosis Center, The First Hospital of Jilin University, Changchun, 130021, China.

There are significant differences in pathology, etiology, clinical features, and treatment options between small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). However, the differences of macrophage distribution and its associated function between SCLC and NSCLC are not fully investigated. Through methods of flow cytometry and cytometric bead array, we examined the levels of various subtypes of macrophages, monocytes, and regulatory T cells (Tregs) as well as interleukin (IL)-10 in bronchoalveolar lavage fluid (BALF) of patients with SCLC or NSCLC. Read More

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http://dx.doi.org/10.1007/s00262-020-02639-zDOI Listing

A single-valent long-acting human CD47 antagonist enhances antibody directed phagocytic activities.

Cancer Immunol Immunother 2020 Jun 24. Epub 2020 Jun 24.

School of Pharmacy, Shanghai JiaoTong University, Shanghai, People's Republic of China.

Many cancer cells express CD47 as a 'don't eat me' signal to mask their presences from immune recognition and destruction. Such a signal is transmitted when CD47 binds to the signal regulatory protein-α (SIRPα) on macrophages to cut the phagocytic reaction. Most recent studies have focused on developing CD47 blocking agents with different affinities and avidities in order to optimize the therapeutic window between efficacy and toxicities involving normal cells expressing CD47. Read More

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http://dx.doi.org/10.1007/s00262-020-02640-6DOI Listing

Anlotinib optimizes anti-tumor innate immunity to potentiate the therapeutic effect of PD-1 blockade in lung cancer.

Cancer Immunol Immunother 2020 Jun 23. Epub 2020 Jun 23.

Department of Integrative Oncology, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, Tianjin, 300060, China.

Background: Many anti-angiogenic agents have the potential to modulate the tumor microenvironment and improve immunotherapy. Anlotinib has demonstrated anti-tumor efficacy in non-small cell lung cancer (NSCLC) in third-line clinical trials. However, its roles in immune regulation and potentially synergistic anti-tumor effect in combination with immune checkpoint inhibition remain unclear. Read More

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http://dx.doi.org/10.1007/s00262-020-02641-5DOI Listing

Prognostic impacts of tumoral expression and serum levels of PD-L1 and CTLA-4 in colorectal cancer patients.

Cancer Immunol Immunother 2020 Jun 23. Epub 2020 Jun 23.

Department of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan.

Background: Programmed cell death ligand-1 (PD-L1) and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) play a pivotal role in cancer immunotherapy. Each of these molecules has a membrane-bound receptor form (mPD-L1/mCTLA-4) and a soluble form (sPD-L1/sCTLA-4). However, these prognostic impacts in colorectal cancer (CRC) remain unclear. Read More

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http://dx.doi.org/10.1007/s00262-020-02645-1DOI Listing

Variation in neutrophil to lymphocyte ratio (NLR) as predictor of outcomes in metastatic renal cell carcinoma (mRCC) and non-small cell lung cancer (mNSCLC) patients treated with nivolumab.

Cancer Immunol Immunother 2020 Jun 19. Epub 2020 Jun 19.

Medical Oncology Department, Hôpital Européen Georges Pompidou, Paris, France.

Background: An elevated pre-treatment neutrophil to lymphocytes ratio (NLR) is associated with poor prognosis in various malignancies. Optimal cut-off is highly variable across studies and could not be determined individually for a patient to inform his prognosis. We hypothesize that NLR variations could be more useful than baseline NLR to predict progression-free survival (PFS) and overall survival (OS) in patients (pts) receiving anti-PD1 treatment. Read More

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http://dx.doi.org/10.1007/s00262-020-02637-1DOI Listing

The role of myeloid-derived suppressor cells in increasing cancer stem-like cells and promoting PD-L1 expression in epithelial ovarian cancer.

Cancer Immunol Immunother 2020 Jun 19. Epub 2020 Jun 19.

Departments of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.

The aim of this study was to investigate the role of myeloid-derived suppressor cells (MDSC) in the induction of cancer stem-like cells (CSC) and programmed death ligand 1 (PD-L1) expression in ovarian cancer. CSC were defined as tumor cells expressing high levels of aldehyde dehydrogenase 1 (ALDH 1). We inoculated G-CSF-expressing or Mock-expressing ovarian cancer cells into mice, and the frequencies of MDSC and CSC in tumors of these models were compared by flow cytometry. Read More

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http://dx.doi.org/10.1007/s00262-020-02628-2DOI Listing

The adjuvant effect of melanin is superior to incomplete Freund's adjuvant in subunit/peptide vaccines in mice.

Cancer Immunol Immunother 2020 Jun 19. Epub 2020 Jun 19.

PARCC, INSERM, UMR-970, Université de Paris, 56 rue Leblanc, 75015, Paris, France.

Peptide vaccines represent an attractive alternative to conventional anti-tumor therapies, but have not yet achieved significant clinical efficacy with commonly used formulations. Combination of short antigenic peptides, synthetic melanin and TLR9 agonist (Toll-like receptor 9, CpG-28) was reported as highly efficient to trigger strong CD8 + T-cell responses. We compared this vaccine approach to the standard adjuvant formulation that combines the incomplete Freund's adjuvant (IFA) and CpG-28, using either an ovalbumin epitope (pOVA30) or a spontaneously occurring tumor neoepitope (mAdpgk). Read More

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http://dx.doi.org/10.1007/s00262-020-02631-7DOI Listing

Current trends in cancer immunotherapy: a literature-mining analysis.

Cancer Immunol Immunother 2020 Jun 15. Epub 2020 Jun 15.

Institute for Language and Speech Processing, Athena Research Center, Xanthi, Greece.

Cancer immunotherapy is a rapidly growing field that is completely transforming oncology care. Mining this knowledge base for biomedically important information is becoming increasingly challenging, due to the expanding number of scientific publications, and the dynamic evolution of this subject with time. In this study, we have employed a literature-mining approach that was used to analyze the cancer immunotherapy-related publications listed in PubMed and quantify emerging trends. Read More

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http://dx.doi.org/10.1007/s00262-020-02630-8DOI Listing

Functional effects of immune complexes formed between pembrolizumab and patient-generated anti-drug antibodies.

Cancer Immunol Immunother 2020 Jun 16. Epub 2020 Jun 16.

Mackenzie Cancer Research Group, Departments of Medicine and Pathology and Biomedical Science, University of Otago Christchurch, Christchurch, New Zealand.

The PD-1-targeting IgG antibody pembrolizumab has significant anti-tumor activity in a proportion of stage IV melanoma patients. A subset of patients develop anti-drug antibodies (ADA) which can form immune complexes (IC) with pembrolizumab. Although IC can induce powerful, Fc-mediated, immune-regulatory effects, their functional impact during pembrolizumab treatment is unclear. Read More

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http://dx.doi.org/10.1007/s00262-020-02636-2DOI Listing

Factors associated with ocular adverse event after immune checkpoint inhibitor treatment.

Cancer Immunol Immunother 2020 Jun 17. Epub 2020 Jun 17.

Department of Ophthalmology, Institute of Vision Research, Severance Hospital, Yonsei University College of Medicine, Yonsei-ro 50-1, Seodaemun-gu, Seoul, Republic of Korea.

Ocular adverse events (OAEs) including vision-threatening intraocular inflammation after immune checkpoint inhibitor (ICI) treatment have been increasingly reported; however, the risk factors associated with OAEs remain elusive. Here, we determined the factors associated with OAEs after ICI treatment. We analyzed 40 consecutive patients who experienced OAEs after ICI treatments. Read More

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http://dx.doi.org/10.1007/s00262-020-02635-3DOI Listing

Correction to: Expression of the immune checkpoint VISTA in breast cancer.

Cancer Immunol Immunother 2020 Jun 18. Epub 2020 Jun 18.

Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No.1 Shuaifuyuan, Dongcheng District, Beijing, 100730, China.

The original version of this article unfortunately contained a mistake. The correct information is given below. Read More

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http://dx.doi.org/10.1007/s00262-020-02602-yDOI Listing

Correction to: Human ovarian cancer intrinsic mechanisms regulate lymphocyte activation in response to immune checkpoint blockade.

Cancer Immunol Immunother 2020 Jun 18. Epub 2020 Jun 18.

Bioscience, Early Oncology R&D, AstraZeneca, Cambridge, UK.

The original version of this article unfortunately contained a mistake. Complete figure captions are missing. Read More

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http://dx.doi.org/10.1007/s00262-020-02601-zDOI Listing

Anti-tumor efficacy of plasmid encoding emm55 in a murine melanoma model.

Cancer Immunol Immunother 2020 Jun 18. Epub 2020 Jun 18.

Department of Cutaneous Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA.

Emm55 is a bacterial gene derived from Streptococcus pyogenes (S. pyogenes) that was cloned into a plasmid DNA vaccine (pAc/emm55). In this study, we investigated the anti-tumor efficacy of pAc/emm55 in a B16 murine melanoma model. Read More

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http://dx.doi.org/10.1007/s00262-020-02634-4DOI Listing

Phase I trial evaluating safety and efficacy of intratumorally administered inflammatory allogeneic dendritic cells (ilixadencel) in advanced gastrointestinal stromal tumors.

Cancer Immunol Immunother 2020 Jun 13. Epub 2020 Jun 13.

Section of Endocrine and Sarcoma Surgery, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.

Background: The majority of patients with advanced gastrointestinal stromal tumor (GIST) develop resistance to imatinib, and subsequent treatments have limited efficacy. Ilixadencel (allogeneic inflammatory dendritic cells) is a cell-based immune primer injected intratumorally that previously has been clinically investigated in metastatic renal cell carcinoma and hepatocellular carcinoma.

Methods: The trial was a single arm phase I trial assessing safety and efficacy of ilixadencel in subjects with progressing advanced/metastatic GIST despite ongoing treatment with second or later lines of tyrosine kinase inhibitors (TKI). Read More

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http://dx.doi.org/10.1007/s00262-020-02625-5DOI Listing

Clinicopathological factors associated with tumor-infiltrating lymphocyte reactivity in breast cancer.

Cancer Immunol Immunother 2020 Jun 11. Epub 2020 Jun 11.

Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea.

Background: The clinical significance of adoptive tumor-infiltrating lymphocyte (TIL) therapy has been demonstrated in many clinical trials. We analyzed the in vitro reactivity of cultured TILs against autologous breast cancer cells.

Methods: TILs and cancer cells were cultured from 31 breast tumor tissues. Read More

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http://dx.doi.org/10.1007/s00262-020-02633-5DOI Listing
June 2020
3.941 Impact Factor

IL-6-induced CD39 expression on tumor-infiltrating NK cells predicts poor prognosis in esophageal squamous cell carcinoma.

Cancer Immunol Immunother 2020 Jun 10. Epub 2020 Jun 10.

Biotherapy Center, the First Affiliated Hospital of Zhengzhou University, 1 Jianshe East Road, Zhengzhou, 450052, Henan, People's Republic of China.

Natural killer (NK) cells, a predominant innate lymphocyte subset, mediates eradicating malignant cells. Purinergic signaling by ectonucleotidase CD39 can suppress T-cell response in caner. However, the role of CD39 in NK cells has not been fully elucidated. Read More

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http://dx.doi.org/10.1007/s00262-020-02629-1DOI Listing
June 2020
3.941 Impact Factor

Metabolomic profiling of tumor-infiltrating macrophages during tumor growth.

Cancer Immunol Immunother 2020 Jun 9. Epub 2020 Jun 9.

Meikai University Research Institute of Odontology (M-RIO), Saitama, Japan.

Myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs) are both key immunosuppressive cells that contribute to tumor growth. Metabolism and immunity of tumors depend on the tumor microenvironment (TME). However, the intracellular metabolism of MDSCs and TAMs during tumor growth remains unclear. Read More

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http://dx.doi.org/10.1007/s00262-020-02622-8DOI Listing
June 2020
3.941 Impact Factor

ADRB3 expression in tumor cells is a poor prognostic factor and promotes proliferation in non-small cell lung carcinoma.

Cancer Immunol Immunother 2020 Jun 8. Epub 2020 Jun 8.

Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou, China.

The cross-talk between cancer cells and monocyte-derived alveolar macrophages (Mo-AMs) promotes non-small cell lung carcinoma (NSCLC) progression. In this study, we report that both cancer cells and Mo-AMs robustly express beta 3-adrenergic receptor (ADRB3) in NSCLC. ADRB3 supports lung cancer cells proliferation and promotes chronic inflammation. Read More

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http://dx.doi.org/10.1007/s00262-020-02627-3DOI Listing

CD200 is overexpressed in neuroblastoma and regulates tumor immune microenvironment.

Cancer Immunol Immunother 2020 Jun 8. Epub 2020 Jun 8.

Pediatric Translational Medicine Institute, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Patients with pediatric cancers such as neuroblastoma (NB) are often unresponsive to checkpoint blockade immunotherapy. One major factor in pediatric tumor resistance to immunotherapy is considered to be the low mutation rate of pediatric tumors. Another factor may be the overexpression of additional inhibitory pathways. Read More

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http://dx.doi.org/10.1007/s00262-020-02589-6DOI Listing

Micro-environmental cross-talk in an organotypic human melanoma-in-skin model directs M2-like monocyte differentiation via IL-10.

Cancer Immunol Immunother 2020 Jun 7. Epub 2020 Jun 7.

Department of Molecular Cell Biology and Immunology, Amsterdam UMC, Vrije Universiteit, Amsterdam, The Netherlands.

Preclinical assessment of novel therapies to fight cancer requires models that reflect the human physiology and immune response. Here, we established an in vitro three-dimensional (3D) reconstructed organotypic human melanoma-in-skin (Mel-RhS) model to investigate cellular and molecular features of tumor formation over a period of 6 weeks. Tumor nests developed over time at the epidermal-dermal junction and spread towards the dermis, in places disrupting the basement membrane. Read More

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http://dx.doi.org/10.1007/s00262-020-02626-4DOI Listing

Combination of cyclin-dependent kinase and immune checkpoint inhibitors for the treatment of bladder cancer.

Cancer Immunol Immunother 2020 Jun 6. Epub 2020 Jun 6.

Division of Hematology and Oncology, Department of Internal Medicine, School of Medicine, University of California Davis, Sacramento, CA, 95817, USA.

Background: Perturbation of the CDK4/6 pathway is frequently observed in advanced bladder cancer. We investigated the potential of targeting this pathway alone or in combination with chemotherapy or immunotherapy as a therapeutic approach for the treatment of bladder cancer METHODS: The genetic alterations of the CDK4/6 pathway in bladder cancer were first analyzed with The Cancer Genome Atlas database and validated in our bladder cancer patient-derived tumor xenografts (PDXs). Bladder cancer cell lines and mice carrying PDXs with the CDK4/6 pathway perturbations were treated with a CDK4/6 inhibitor palbociclib to determine its anticancer activity and the underlying mechanisms. Read More

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http://dx.doi.org/10.1007/s00262-020-02609-5DOI Listing

Infiltration of T cells promotes the metastasis of ovarian cancer cells via the modulation of metastasis-related genes and PD-L1 expression.

Cancer Immunol Immunother 2020 Jun 5. Epub 2020 Jun 5.

Department of Obstetrics and Gynaecology, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, Special Administrative Region of China.

Due to its high ability to disseminate, ovarian cancer remains one of the largest threats to women's health, worldwide. Evidence showed that the immune cells infiltrating the tumor microenvironment are crucial in mediating metastasis. Therefore, it is necessary to understand which types of immune cells are involved in metastasis, and to determine the mechanisms by which they influence the process. Read More

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http://dx.doi.org/10.1007/s00262-020-02621-9DOI Listing

Influence of antigen density and immunosuppressive factors on tumor-targeted costimulation with antibody-fusion proteins and bispecific antibody-mediated T cell response.

Cancer Immunol Immunother 2020 Jun 5. Epub 2020 Jun 5.

Institute of Cell Biology and Immunology, University of Stuttgart, Allmandring 31, 70569, Stuttgart, Germany.

Target expression heterogeneity and the presence of an immunosuppressive microenvironment can hamper severely the efficiency of immunotherapeutic approaches. We have analyzed the potential to encounter and overcome such conditions by a combinatory two-target approach involving a bispecific antibody retargeting T cells to tumor cells and tumor-directed antibody-fusion proteins with costimulatory members of the B7 and TNF superfamily. Targeting the tumor-associated antigens EpCAM and EGFR with the bispecific antibody and costimulatory fusion proteins, respectively, we analyzed the impact of target expression and the influence of the immunosuppressive factors IDO, IL-10, TGF-β, PD-1 and CTLA-4 on the targeting-mediated stimulation of T cells. Read More

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http://dx.doi.org/10.1007/s00262-020-02624-6DOI Listing

Cell composition and expansion strategy can reduce the beneficial effect of AKT-inhibition on functionality of CD8 T cells.

Cancer Immunol Immunother 2020 Jun 5. Epub 2020 Jun 5.

Department of Laboratory Medicine, Laboratory of Hematology, Radboud Institute of Molecular Life Sciences, Radboud university medical center, Geert Grooteplein Zuid 8, 6525 GA, Nijmegen, The Netherlands.

AKT-inhibition is a promising approach to improve T cell therapies; however, its effect on CD4 T cells is insufficiently explored. Previously, we and others showed that AKT-inhibition during ex vivo CD8 T cell expansion facilitates the generation of polyfunctional T cells with stem cell memory-like traits. However, most therapeutic T cell products are generated from lymphocytes, containing CD4 T cells that can affect CD8 T cells dependent on the Th-subset. Read More

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http://dx.doi.org/10.1007/s00262-020-02612-wDOI Listing

Exploratory open-label clinical study to determine the S-588410 cancer peptide vaccine-induced tumor-infiltrating lymphocytes and changes in the tumor microenvironment in esophageal cancer patients.

Cancer Immunol Immunother 2020 Jun 4. Epub 2020 Jun 4.

Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan.

Cancer vaccines induce cancer-specific T-cells capable of eradicating cancer cells. The impact of cancer peptide vaccines (CPV) on the tumor microenvironment (TME) remains unclear. S-588410 is a CPV comprising five human leukocyte antigen (HLA)-A*24:02-restricted peptides derived from five cancer testis antigens, DEPDC1, MPHOSPH1, URLC10, CDCA1 and KOC1, which are overexpressed in esophageal cancer. Read More

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http://dx.doi.org/10.1007/s00262-020-02619-3DOI Listing

Pro-tumorigenic functions of macrophages at the primary, invasive and metastatic tumor site.

Cancer Immunol Immunother 2020 Jun 4. Epub 2020 Jun 4.

Research Center for Immunodeficiencies, Children's Medical Center, Tehran University of Medical Sciences, Dr Qarib St, Keshavarz Blvd, 14194, Tehran, Iran.

The tumor microenvironment (TME) not only facilitates cancer progression from the early formation to distant metastasis, but also it differs itself from time to time alongside the tumor evolution. Tumor-associated macrophages (TAMs), whether as pre-existing tissue-resident macrophages or recruited monocytes, are an inseparable part of this microenvironment. As their parents are broadly classified into a dichotomic, simplistic M1 and M2 subtypes, TAMs also exert paradoxical and diverse phenotypes as they are settled in different regions of TME and receive different microenvironmental signals. Read More

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http://dx.doi.org/10.1007/s00262-020-02616-6DOI Listing
June 2020
3.941 Impact Factor

Expression profiles and function of IL6 in polymorphonuclear myeloid-derived suppressor cells.

Cancer Immunol Immunother 2020 Jun 1. Epub 2020 Jun 1.

Department of Biochemistry and Molecular Biology, Medical College of Georgia, 1410 Laney Walker Blvd, Augusta, GA, 30912, USA.

IL6 is an inflammatory cytokine with pleiotropic functions in both immune and nonimmune cells, and its expression level is inversely correlated with disease prognosis in patients with cancer. However, blocking IL6 alone has only yielded minimal efficacy in human cancer patients. We aimed at defining IL6 expression profiles under inflammatory conditions and cancer, and elucidating the mechanism underlying IL6 intrinsic signaling in colon carcinoma. Read More

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http://dx.doi.org/10.1007/s00262-020-02620-wDOI Listing

Differences in PD-1 expression on CD8+ T-cells in chronic myeloid leukemia patients according to disease phase and TKI medication.

Cancer Immunol Immunother 2020 May 30. Epub 2020 May 30.

Department of Hematology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.

Malignant cells can increase in number using immune escape mechanisms such as immune checkpoints. In this study, we evaluated the expression of an immune checkpoint programmed death 1 (PD-1) on T-cell subsets in chronic myeloid leukemia (CML). We obtained bone marrow aspirate samples from CML patients and from individuals without evidence of hematologic malignancies (controls). Read More

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http://dx.doi.org/10.1007/s00262-020-02617-5DOI Listing

Clinicopathologic correlates of first-line pembrolizumab effectiveness in patients with advanced NSCLC and a PD-L1 expression of ≥ 50%.

Cancer Immunol Immunother 2020 05 30. Epub 2020 May 30.

Medical Oncology, St. Salvatore Hospital, L'Aquila, Italy.

Background: Single-agent pembrolizumab represents the standard first-line option for metastatic non-small-cell lung cancer (NSCLC) patients with a PD-L1 (programmed death-ligand 1) expression of ≥ 50%.

Methods: We conducted a multicenter retrospective study aimed at evaluating the clinicopathologic correlates of pembrolizumab effectiveness in patients with treatment-naïve NSCLC and a PD-L1 expression of ≥ 50%.

Results: One thousand and twenty-six consecutive patients were included. Read More

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http://dx.doi.org/10.1007/s00262-020-02613-9DOI Listing
May 2020
3.941 Impact Factor

Differences in the sensitivity of classically and alternatively activated macrophages to TAK1 inhibitor-induced necroptosis.

Cancer Immunol Immunother 2020 May 29. Epub 2020 May 29.

Department of Immunology, Faculty of Medicine, University of Debrecen, 1 Egyetem Square, Debrecen, 4032, Hungary.

Controlling the balance of pro-inflammatory M1 versus anti-inflammatory M2 macrophages may have paramount therapeutic benefit in cardiovascular diseases, infections, cancer and chronic inflammation. The targeted depletion of different macrophage populations provides a therapeutic option to regulate macrophage-mediated functions. Macrophages are highly sensitive to necroptosis, a newly described regulated cell death mediated by receptor-interacting serine/threonine-protein kinase 1 (RIPK1), RIPK3 and mixed lineage kinase domain like pseudokinase. Read More

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http://dx.doi.org/10.1007/s00262-020-02623-7DOI Listing

In vitro 4-1BB stimulation promotes expansion of CD8 tumor-infiltrating lymphocytes from various sarcoma subtypes.

Cancer Immunol Immunother 2020 May 29. Epub 2020 May 29.

Department of Oncology, Copenhagen University Hospital Herlev, Herlev, Denmark.

Tumor-specific tumor-infiltrating lymphocytes (TILs) can be in vitro expanded and have the ability to induce complete and durable tumor regression in some patients with melanoma following adoptive cell therapy (ACT). In this preclinical study, we investigated the feasibility of expanding TIL from sarcomas, as well as performing functional in vitro analyses on these. TILs were expanded in vitro by the use of IL2 stimulation with or without the addition of 4-1BB and CD3 antibodies. Read More

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http://dx.doi.org/10.1007/s00262-020-02568-xDOI Listing

NKG2D-Fc fusion protein promotes antitumor immunity through the depletion of immunosuppressive cells.

Cancer Immunol Immunother 2020 May 28. Epub 2020 May 28.

Department of Pathology, The Johns Hopkins University School of Medicine, 1550 Orleans St., CRB II - Room 307, Baltimore, MD, 21287, USA.

A major factor impeding the success of numerous therapeutic approaches in cancer is the immunosuppressive nature of the tumor microenvironment (TME). Hence, methods capable of reverting tumor immunosuppression through depletion or reprogramming of myeloid-derived suppressive cells (MDSCs) and regulatory T cells (Tregs) are of great clinical need. Here, we explore NKG2D-Fc as a modality to modulate antitumor immunity through the depletion of immunosuppressive MDSCs and Tregs in the TME. Read More

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http://dx.doi.org/10.1007/s00262-020-02615-7DOI Listing

Antitumor efficacy of BAFF-R targeting CAR T cells manufactured under clinic-ready conditions.

Cancer Immunol Immunother 2020 May 25. Epub 2020 May 25.

Toni Stephenson Lymphoma Center, Department of Hematology and Hematopoietic Cell Transplantation, Beckman Research Institute of City of Hope, Duarte, CA, 91010, USA.

B-cell malignancies can potentially be cured by CD19 chimeric antigen receptor (CAR) T-cell therapy. Although clinical response rates can be up to 93% in acute lymphoblastic leukemia, treatment-related antigen loss and lack of therapeutic persistence contribute to disease relapse. These shortcomings of current CAR T-cell therapy indicate the need for biologically relevant target selection and for improving the efficacy and persistence of the CAR T cells, which we have addressed by developing a novel B-cell activating factor receptor (BAFF-R) CAR T-cell therapy with improved therapeutic persistence. Read More

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http://dx.doi.org/10.1007/s00262-020-02614-8DOI Listing

Development of CDX-527: a bispecific antibody combining PD-1 blockade and CD27 costimulation for cancer immunotherapy.

Cancer Immunol Immunother 2020 May 25. Epub 2020 May 25.

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

CD27 is a costimulatory molecule that provides a complementary target to the PD-1/PD-L1 checkpoint axis on T cells. Combining a CD27 agonist antibody with PD-1/PD-L1 blockade has shown synergistic antitumor activity in preclinical models, which led to clinical studies of the combination in cancer patients. We theorized that coupling CD27 costimulation with PD-1/PD-L1 blockade in a bispecific antibody (BsAb) may provide greater immune activating properties than combining the individual mAbs due to enhanced CD27 activation by cross-linking through PD-L1 and Fc receptors. Read More

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http://dx.doi.org/10.1007/s00262-020-02610-yDOI Listing

PD-L1 expression correlates with tumor-infiltrating lymphocytes and better prognosis in patients with HPV-negative head and neck squamous cell carcinomas.

Cancer Immunol Immunother 2020 May 24. Epub 2020 May 24.

Department of Otolaryngology, Hospital Universitario Central de Asturias and Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Instituto Universitario de Oncología del Principado de Asturias, University of Oviedo, 33011, Oviedo, Spain.

Introduction: The importance of immune tumor microenvironment in the prognosis of patients with head and neck squamous carcinomas (HNSCC) is increasingly recognized. We analyzed the prognostic relevance of PD-L1 and PD-1 expressions in relation to the infiltration by CD8 and FOXP3 tumor-infiltrating lymphocytes (TILs).

Methods: Samples from 372 surgically treated HPV-negative HNSCC patients were evaluated by immunohistochemistry for PD-L1 expression [both tumor proportion score (TPS) and combined proportion score (CPS)], PD-1 expression in immune cells, and density of infiltrating CD8 and FOXP3 TILs. Read More

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http://dx.doi.org/10.1007/s00262-020-02604-wDOI Listing

Systemic but not MDSC-specific IRF4 deficiency promotes an immunosuppressed tumor microenvironment in a murine pancreatic cancer model.

Cancer Immunol Immunother 2020 May 24. Epub 2020 May 24.

Center of Integrated Protein Science Munich (CIPSM) and Division of Clinical Pharmacology, University Hospital, LMU Munich, Munich, Germany.

Pancreatic ductal adenocarcinoma is characterized by a strong immunosuppressive network with a dense infiltration of myeloid cells including myeloid-derived suppressor cells (MDSC). Two distinct populations of MDSC have been defined: polymorphonuclear MDSC (PMN-MDSC) and monocytic MDSC (M-MDSC). Several factors influence the development and function of MDSC including the transcription factor interferon regulatory factor 4 (IRF4). Read More

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http://dx.doi.org/10.1007/s00262-020-02605-9DOI Listing

A TLR4-TRIF-dependent signaling pathway is required for protective natural tumor-reactive IgM production by B1 cells.

Cancer Immunol Immunother 2020 May 24. Epub 2020 May 24.

Department of Microbiology and Immunology, Wake Forest School of Medicine, 575 N. Patterson Ave., Winston-Salem, NC, 27101, USA.

Metastatic cancer involving spread to the peritoneal cavity is referred to as peritoneal carcinomatosis and has a very poor prognosis. Our previous studies demonstrated a toll-like receptor 4 (TLR4) and C-type lectin receptor (CLR; Mincle/MCL) agonist pairing of monophosphoryl lipid A (MPL) and trehalose-6,6'-dicorynomycolate (TDCM) effectively inhibits peritoneal tumor growth and ascites development through a mechanism dependent upon B1a cell-produced natural IgM, complement, and phagocytes. In the current study, we investigated the requirement for TLR4 and Fc receptor common γ chain (FcRγ), required for Mincle/MCL signaling, in the MPL/TDCM-elicited response. Read More

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http://dx.doi.org/10.1007/s00262-020-02607-7DOI Listing

Primary breast tumours but not lung metastases induce protective anti-tumour immune responses after Treg-depletion.

Cancer Immunol Immunother 2020 May 23. Epub 2020 May 23.

Division of Infection and Immunity, Cardiff University School of Medicine, SIURI, Cardiff, CF14 4XN, UK.

Although metastatic disease is responsible for the majority of cancer deaths, tests of novel immunotherapies in mouse tumour models often focus on primary tumours without determining whether these therapies also target metastatic disease. This study examined the impact of depleting Foxp3 regulatory T cells (Treg), on lung metastases, using a mouse model of breast cancer. After Treg-depletion, generation of an immune response to the primary tumour was a critical determinant for limiting development of metastasis. Read More

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http://dx.doi.org/10.1007/s00262-020-02603-xDOI Listing

Immune checkpoint inhibitors reverse tolerogenic mechanisms induced by melanoma targeted radionuclide therapy.

Cancer Immunol Immunother 2020 May 23. Epub 2020 May 23.

UMR1240 INSERM, Université Clermont Auvergne, 58, rue Montalembert, BP 184, 63005, Clermont-Ferrand, France.

In line with the ongoing phase I trial (NCT03784625) dedicated to melanoma targeted radionuclide therapy (TRT), we explore the interplay between immune system and the melanin ligand [I]ICF01012 alone or combined with immunotherapy (immune checkpoint inhibitors, ICI) in preclinical models. Here we demonstrate that [I]ICF01012 induces immunogenic cell death, characterized by a significant increase in cell surface-exposed annexin A1 and calreticulin. Additionally, [I]ICF01012 increases survival in immunocompetent mice, compared to immunocompromised (29 vs. Read More

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http://dx.doi.org/10.1007/s00262-020-02606-8DOI Listing

Expression of programmed death-ligand 1 (PD-L1) in human pituitary neuroendocrine tumor.

Cancer Immunol Immunother 2020 May 22. Epub 2020 May 22.

Laboratoire MITOVASC, UMR CNRS 6015, INSERM 1083, University of Angers, Angers, France.

Objective: To explore the programmed death-ligand 1 (PD-L1) expression in varied subtypes of pituitary neuroendocrine tumors with assessment of their clinical behavior at diagnosis and follow-up.

Methods: We conducted a retrospective monocentric study, including all patients operated in the Academic Hospital of Angers (France) for a pituitary neuroendocrine tumor between 2012 and 2018. PDL-1 immunostaining was performed using a European Conformity-In Vitro Diagnostic-labeled anti-PDL1 antibody (clone 22C3). Read More

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http://dx.doi.org/10.1007/s00262-020-02611-xDOI Listing

Selective targeting of different populations of myeloid-derived suppressor cells by histone deacetylase inhibitors.

Cancer Immunol Immunother 2020 May 20. Epub 2020 May 20.

Immunology, Microenvironment and Metastasis Program, The Wistar Institute, Rm. 118, 3601 Spruce Str., Philadelphia, PA, 19104, USA.

Myeloid-derived suppressor cells (MDSCs) are widely implicated in negative regulation of immune responses in cancer. Inhibition of class I histone deacetylases (HDAC) with entinostat has anti-MDSC activity. However, as single agent, it did not delay tumor growth in EL4 and LLC tumor models. Read More

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http://dx.doi.org/10.1007/s00262-020-02588-7DOI Listing