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    4422 results match your criteria Cancer immunology immunotherapy : CII[Journal]

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    Cancer vaccine strategies: translation from mice to human clinical trials.
    Cancer Immunol Immunother 2017 Nov 15. Epub 2017 Nov 15.
    Vaccine Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
    We translated two cancer vaccine strategies from mice into human clinical trials. (1) In preclinical studies on TARP, an antigen expressed in most prostate cancers, we mapped epitopes presented by HLA-A*0201, modified them to increase affinity and immunogenicity in HLA transgenic mice, and induced human T cells that killed human cancer cells ("epitope enhancement"). In a clinical trial, HLA-A2(+) prostate cancer patients with PSA biochemical recurrence (Stage D0) were vaccinated with two peptides either in Montanide-ISA51 or on autologous dendritic cells (DCs). Read More

    Targeting and suppression of HER3-positive breast cancer by T lymphocytes expressing a heregulin chimeric antigen receptor.
    Cancer Immunol Immunother 2017 Nov 10. Epub 2017 Nov 10.
    Department of Biochemistry and Molecular Biology, Fourth Military Medical University, 169 Changle West Road, Xi'an, 710032, Shaanxi, China.
    Chimeric antigen receptor-modulated T lymphocytes (CAR-T) have emerged as a powerful tool for arousing anticancer immunity. Endogenous ligands for tumor antigen may outperform single-chain variable fragments to serve as a component of CARs with high cancer recognition efficacy and minimized immunogenicity. As heterodimerization and signaling partners for human epidermal growth factor receptor 2 (HER2), HER3/HER4 has been implicated in tumorigenic signaling and therapeutic resistance of breast cancer. Read More

    The class I/IV HDAC inhibitor mocetinostat increases tumor antigen presentation, decreases immune suppressive cell types and augments checkpoint inhibitor therapy.
    Cancer Immunol Immunother 2017 Nov 9. Epub 2017 Nov 9.
    Mirati Therapeutics, Inc., 9393 Towne Center Dr, Suite 200, San Diego, CA, 92121, USA.
    Checkpoint inhibitor therapy has led to major treatment advances for several cancers including non-small cell lung cancer (NSCLC). Despite this, a significant percentage of patients do not respond or develop resistance. Potential mechanisms of resistance include lack of expression of programmed death ligand 1 (PD-L1), decreased capacity to present tumor antigens, and the presence of an immunosuppressive tumor microenvironment. Read More

    Prophylactic DNA vaccine targeting Foxp3(+) regulatory T cells depletes myeloid-derived suppressor cells and improves anti-melanoma immune responses in a murine model.
    Cancer Immunol Immunother 2017 Nov 9. Epub 2017 Nov 9.
    Department of Immunology, Building No. 7, School of Medicine, Tehran University of Medical Sciences, Poursina Avenue, Tehran, 14155-6447, Iran.
    Regulatory T cells (Treg) and myeloid-derived suppressor cells (MDSC) are the two important and interactive immunosuppressive components of the tumor microenvironment that hamper anti-tumor immune responses. Therefore, targeting these two populations together might be beneficial for overcoming immune suppression in the tumor microenvironment. We have recently shown that prophylactic Foxp3 DNA/recombinant protein vaccine (Foxp3 vaccine) promotes immunity against Treg in tumor-free conditions. Read More

    Tumor-derived high-mobility group box 1 and thymic stromal lymphopoietin are involved in modulating dendritic cells to activate T regulatory cells in a mouse model.
    Cancer Immunol Immunother 2017 Nov 7. Epub 2017 Nov 7.
    Department of Dermatology, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15213, USA.
    High-mobility group box 1 (HMGB1) is involved in the tumor-associated activation of regulatory T cells (Treg), but the mechanisms remain unknown. In a mouse tumor model, silencing HMGB1 in tumor cells or inhibiting tumor-derived HMGB1 not only dampened the capacity of tumor cells to produce thymic stromal lymphopoietin (TSLP), but also aborted the tumor-associated modulation of Treg-activating DC. Tumor-derived HMGB1 triggered the production of TSLP by tumor cells. Read More

    BRAF peptide vaccine facilitates therapy of murine BRAF-mutant melanoma.
    Cancer Immunol Immunother 2017 Nov 1. Epub 2017 Nov 1.
    Division of Pharmacoengineering and Molecular Pharmaceutics and Center for Nanotechnology in Drug Delivery, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, 1315 Kerr Hall, Campus Box 7571, Chapel Hill, NC, 27599, USA.
    Approximately, 50% of human melanomas are driven by BRAF mutations, which produce tumors that are highly immunosuppressive and often resistant to vaccine therapy. We introduced lipid-coated calcium phosphate nanoparticles (LCP NPs) as a carrier to efficiently deliver a tumor-specific antigen, the BRAF(V600E) peptide, to drive dendritic cell (DC) maturation and antigen presentation in C57BL6 mice. The BRAF peptide vaccine elicited a robust, antigen-specific cytotoxic T cell response and potent tumor growth inhibition in a murine BRAF-mutant melanoma model. Read More

    A phase I vaccination study with dendritic cells loaded with NY-ESO-1 and α-galactosylceramide: induction of polyfunctional T cells in high-risk melanoma patients.
    Cancer Immunol Immunother 2017 Nov 1. Epub 2017 Nov 1.
    Malaghan Institute of Medical Research, PO Box 7060, Wellington, 6242, New Zealand.
    Vaccines that elicit targeted tumor antigen-specific T-cell responses have the potential to be used as adjuvant therapy in patients with high risk of relapse. However, the responses induced by vaccines in cancer patients have generally been disappointing. To improve vaccine function, we investigated the possibility of exploiting the immunostimulatory capacity of type 1 Natural killer T (NKT) cells, a cell type enriched in lymphoid tissues that can trigger improved antigen-presenting function in dendritic cells (DCs). Read More

    Cross-talk between TNF-α and IFN-γ signaling in induction of B7-H1 expression in hepatocellular carcinoma cells.
    Cancer Immunol Immunother 2017 Oct 31. Epub 2017 Oct 31.
    Department of Immunology and Key Laboratory of Infection and Immunity of Shandong Province, Shandong University School of Basic Medical Sciences, 44# Wenhua Xi Road, Jinan, 250012, China.
    Clinical benefit from immunotherapy of B7-H1/PD-1 checkpoint blockade indicates that it is important to understand the regulatory mechanism of B7-H1 expression in cancer cells. As an adaptive response to the endogenous antitumor immunity, B7-H1 expression is up-regulated in HCC cells. B7-H1 expression is induced mainly by IFN-γ released from tumor-infiltrating T cells in HCC. Read More

    CXCL13 expression is prognostic and predictive for postoperative adjuvant chemotherapy benefit in patients with gastric cancer.
    Cancer Immunol Immunother 2017 Oct 31. Epub 2017 Oct 31.
    Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Room 358, Building West 7, 130 Dongan Rd, Shanghai, 200032, China.
    Background: Chemokine (C-X-C motif) ligand 13 (CXCL13/BLC/BCA-1) is a cytokine from C-X-C chemokine family, which is selectively chemotactic for B cells. Previous research has demonstrated that high CXCL13 expression is correlated to poor prognosis in various cancers. However, the association between CXCL13 expression and gastric cancer is still unclear. Read More

    A CD3-bispecific molecule targeting P-cadherin demonstrates T cell-mediated regression of established solid tumors in mice.
    Cancer Immunol Immunother 2017 Oct 24. Epub 2017 Oct 24.
    Oncology Research and Development Pfizer Inc., La Jolla, CA, USA.
    Strong evidence exists supporting the important role T cells play in the immune response against tumors. Still, the ability to initiate tumor-specific immune responses remains a challenge. Recent clinical trials suggest that bispecific antibody-mediated retargeted T cells are a promising therapeutic approach to eliminate hematopoietic tumors. Read More

    NY-ESO-1- and survivin-specific T-cell responses in the peripheral blood from patients with glioma.
    Cancer Immunol Immunother 2017 Oct 20. Epub 2017 Oct 20.
    Therapeutic Immunology, F79, Department of Laboratory Medicine, Karolinska University Hospital Huddinge, Karolinska Institutet, Hälsovägen, Huddinge, 14186, Stockholm, Sweden.
    The prognosis for patients with glioblastoma is grim. Ex vivo expanded tumor-associated antigen (TAA)-reactive T-cells from patients with glioma may represent a viable source for anticancer-directed cellular therapies. Immunohistochemistry was used to test the survivin (n = 40 samples) and NY-ESO-1 (n = 38 samples) protein expression in tumor specimens. Read More

    Clinical and immunologic evaluation of three metastatic melanoma patients treated with autologous melanoma-reactive TCR-transduced T cells.
    Cancer Immunol Immunother 2017 Oct 20. Epub 2017 Oct 20.
    Department of Surgery, Loyola University Chicago, 2160 S. 1st Avenue, Maywood, IL, 60153, USA.
    Malignant melanoma incidence has been increasing for over 30 years, and despite promising new therapies, metastatic disease remains difficult to treat. We describe preliminary results from a Phase I clinical trial (NCT01586403) of adoptive cell therapy in which three patients received autologous CD4(+) and CD8(+) T cells transduced with a lentivirus carrying a tyrosinase-specific TCR and a marker protein, truncated CD34 (CD34t). This unusual MHC Class I-restricted TCR produces functional responses in both CD4(+) and CD8(+) T cells. Read More

    Absolute lymphocyte counts at end of induction correlate with distinct immune cell compartments in pediatric B cell precursor acute lymphoblastic leukemia.
    Cancer Immunol Immunother 2017 Oct 20. Epub 2017 Oct 20.
    Michael Cuccione Childhood Cancer Research Program, BC Children's Hospital Research Institute, 950 West 28th Avenue, Reid Lab (Room 3062), Vancouver, BC, V5Z 4H4, Canada.
    Several retrospective studies in children with B cell precursor (BCP) acute lymphoblastic leukemia (ALL) provided clinical evidence that higher absolute lymphocyte counts (ALC) early into treatment significantly correlated with improved relapse-free and overall survival. It still remains unknown, however, whether the predictive role of higher ALCs reflects general bone marrow recovery or a more specific attribute of immune function. To investigate this question, we implemented a prospective observational cohort study in 20 children with BCP ALL on day 29 (D29) of induction chemotherapy and immunophenotyped their lymphoid (T, B and natural killer cells) and myeloid (neutrophils, monocytes, dendritic cells) compartments. Read More

    Immunotherapy for hepatocellular carcinoma patients: is it ready for prime time?
    Cancer Immunol Immunother 2017 Oct 20. Epub 2017 Oct 20.
    Department of Medical Oncology, Dana-Farber Cancer Institute Harvard Medical School, 450 Brookline Avenue, M1B13, Boston, MA, 02215, USA.
    Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and the second most common cause of cancer death worldwide. Current treatment options for patients with intermediate and advanced HCC are limited, and there is an unmet need for novel therapeutic approaches. HCC is an attractive target for immunomodulation therapy, since it arises in an inflammatory milieu due to hepatitis B and C infections and cirrhosis. Read More

    Clinicopathologic implications of CD8(+)/Foxp3(+) ratio and miR-574-3p/PD-L1 axis in spinal chordoma patients.
    Cancer Immunol Immunother 2017 Oct 20. Epub 2017 Oct 20.
    Department of Pathology, The Second Xiangya Hospital, Central South University, Changsha, 410011, China.
    Currently, little is known about the interactions between microRNAs (miRNAs) and the PD-1/PD-L1 signaling pathway in chordoma, and data discussing the role of the immune milieu in chordoma prognosis are limited. We aimed to analyze the relationship between PD-L1, miR-574-3p, microenvironmental tumor-infiltrating lymphocytes (TILs) and clinicopathological features of spinal chordoma patients. PD-L1 expression and TILs (including Foxp3(+), CD8(+), PD-1(+) and PD-L1(+)) were assessed by immunohistochemistry in tumor specimens of 54 spinal chordoma patients. Read More

    Cholecystokinin receptor antagonist alters pancreatic cancer microenvironment and increases efficacy of immune checkpoint antibody therapy in mice.
    Cancer Immunol Immunother 2017 Oct 17. Epub 2017 Oct 17.
    Department of Oncology, Georgetown Lombardi Comprehensive Cancer Center, Georgetown University, Washington DC, USA.
    Advanced pancreatic ductal adenocarcinoma (PDAC) has typically been resistant to chemotherapy and immunotherapy; therefore, novel strategies are needed to enhance therapeutic response. Cholecystokinin (CCK) has been shown to stimulate growth of pancreatic cancer. CCK receptors (CCKRs) are present on pancreatic cancer cells, fibroblasts, and lymphocytes. Read More

    A filamentous bacteriophage targeted to carcinoembryonic antigen induces tumor regression in mouse models of colorectal cancer.
    Cancer Immunol Immunother 2017 Oct 12. Epub 2017 Oct 12.
    Laboratory of Gene Immunotherapy, Fundación Ciencia & Vida, Av. Zañartu 1482, Ñuñoa, 7780272, Santiago, Chile.
    Colorectal cancer is a deadly disease, which is frequently diagnosed at advanced stages, where conventional treatments are no longer effective. Cancer immunotherapy has emerged as a new form to treat different malignancies by turning-on the immune system against tumors. However, tumors are able to evade antitumor immune responses by promoting an immunosuppressive microenvironment. Read More

    Quantification of altered tissue turnover in a liquid biopsy: a proposed precision medicine tool to assess chronic inflammation and desmoplasia associated with a pro-cancerous niche and response to immuno-therapeutic anti-tumor modalities.
    Cancer Immunol Immunother 2017 Oct 11. Epub 2017 Oct 11.
    Nordic Bioscience, Biomarkers & Research, Herlev Hovedgade 205-207, Herlev, Denmark.
    Immuno-therapy has begun to revolutionize cancer treatment. However, despite the significant progress achieved in regard to the duration of clinical benefits, a substantial number of patients do not respond to these therapies. To improve the outcome of patients receiving immuno-therapy, there is a need for novel biomarkers that can predict and monitor treatment. Read More

    Characterization of arthralgia induced by PD-1 antibody treatment in patients with metastasized cutaneous malignancies.
    Cancer Immunol Immunother 2017 Oct 10. Epub 2017 Oct 10.
    Department of Dermatology and National Center for Tumor Diseases, University Hospital Heidelberg, Im Neuenheimer Feld 460, 69120, Heidelberg, Germany.
    Background: PD-1 antibodies (PD1ab) are increasingly used in metastatic melanoma and other malignancies. Arthralgia is an underestimated side effect of PD-1 antibody treatment with unknown cause. Our aim was to characterize PD1ab-induced arthralgia. Read More

    Tumor-infiltrating immune cells as potential biomarkers predicting response to treatment and survival in patients with metastatic melanoma receiving ipilimumab therapy.
    Cancer Immunol Immunother 2017 Oct 7. Epub 2017 Oct 7.
    Department of Surgical and Molecular Pathology, National Institute of Oncology, 7-9. Ráth György u., Budapest, H-1122, Hungary.
    Monoclonal antibodies targeting immune checkpoints are gaining ground in the treatment of melanoma and other cancers, and considerable effort is made to identify biomarkers predicting the efficacy of these therapies. Our retrospective study was performed on surgical tissue samples (52 lymph nodes and 34 cutaneous/subcutaneous metastases) from 30 patients with metastatic melanoma treated with ipilimumab. Using a panel of 11 antibodies against different immune cell types, intratumoral immune cell densities were determined and evaluated in relation to response to ipilimumab treatment and disease outcome. Read More

    Safety of shortened infusion times for combined ipilimumab and nivolumab.
    Cancer Immunol Immunother 2017 Oct 7. Epub 2017 Oct 7.
    Department of Dermatology, Center for Dermatooncology, Eberhard-Karls-University of Tuebingen, Tübingen, Germany.
    Background: Combined ipilimumab and nivolumab induces encouraging response rates in patients with unresectable or metastatic melanoma. However, the approved protocol for dual checkpoint inhibition (3 mg/kg ipilimumab over 90 min and 1 mg/kg nivolumab over 60 min) is time-intensive and several trials have shown that both single agents can be safely administered at faster infusion rates.

    Aim: To investigate whether combined checkpoint inhibition with 3 mg/kg ipilimumab and 1 mg/kg nivolumab can be safely administered over 30 min per agent. Read More

    Ipilimumab and early signs of pulmonary toxicity in patients with metastastic melanoma: a prospective observational study.
    Cancer Immunol Immunother 2017 Oct 5. Epub 2017 Oct 5.
    Department of Pulmonology, University Hospital Zurich, Raemistrasse 100, 8091, Zurich, Switzerland.
    Ipilimumab, an immune checkpoint inhibitor, is approved for treatment metastastic melanoma and is a promising agent against other malignancies. There is some preliminary evidence from case reports that ipilimumab treatment may be associated with pulmonary side effects. However, data from prospective studies on ipilimumab-related pulmonary toxicity are still scarce. Read More

    Immunological classification of renal cell carcinoma patients based on phenotypic analysis of immune check-point molecules.
    Cancer Immunol Immunother 2017 Oct 3. Epub 2017 Oct 3.
    Department of Clinical Research in Tumour Immunology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
    Objectives: To clarify comprehensive immunological signature patterns of tumour tissue-infiltrating lymphocytes in patients with renal cell carcinoma and show its clinical significance.

    Materials And Methods: We investigated the surface marker expressions of tumour tissue-infiltrating lymphocytes quantitatively and classified them based on their functional populations. We extracted 109 sets of tumour tissue-infiltrating lymphocytes from 80 patients who underwent surgical resection of renal cell carcinoma, of which 44 tumour tissue-infiltrating lymphocytes were multiply extracted from 15 patients. Read More

    Daunorubicin conjugated with alpha-fetoprotein selectively eliminates myeloid-derived suppressor cells (MDSCs) and inhibits experimental tumor growth.
    Cancer Immunol Immunother 2017 Sep 27. Epub 2017 Sep 27.
    Laboratory of Molecular Immunology and Immunobiotechnology, M. A. Aitkhozhin's Institute of Molecular Biology and Biochemistry, 86 Dosmukhamedov St., Almaty, 050012, Kazakhstan.
    Failure of antitumor immunity in cancer was shown to be mediated by myeloid-derived suppressor cells (MDSCs), which are considered to be one of the key factors contributing to the development of malignant diseases. Therefore, the development of pharmacological approaches to effectively eliminate MDSCs in organisms carrying growing tumors is a promising pathway for potential treatment. For this purpose we propose alpha-fetoprotein (AFP) conjugated with a cytotoxic agent as a vector molecule, specifically recognizing MDSCs. Read More

    Phase I/II trial of dendritic cell-based active cellular immunotherapy with DCVAC/PCa in patients with rising PSA after primary prostatectomy or salvage radiotherapy for the treatment of prostate cancer.
    Cancer Immunol Immunother 2017 Sep 25. Epub 2017 Sep 25.
    Department of Immunology, Charles University, 2nd Faculty of Medicine and University Hospital Motol, V Uvalu 84, Prague 5, 15005, Prague, Czech Republic.
    Objective: Immunotherapy of cancer has the potential to be effective mostly in patients with a low tumour burden. Rising PSA (prostate-specific antigen) levels in patients with prostate cancer represents such a situation. We performed the present clinical study with dendritic cell (DC)-based immunotherapy in this patient population. Read More

    Clinical evaluation of macrophages in cancer: role in treatment, modulation and challenges.
    Cancer Immunol Immunother 2017 Dec 25;66(12):1509-1527. Epub 2017 Sep 25.
    Cork Cancer Research Centre, Western Gateway Building, University College Cork, Western Road, Cork, Ireland.
    The focus of immunotherapeutics has been placed firmly on anti-tumour T cell responses. Significant progress has been made in the treatment of both local and systemic malignancies, but low response rates and rising toxicities are limiting this approach. Advancements in the understanding of tumour immunology are opening up a new range of therapeutic targets, including immunosuppressive factors in the tumour microenvironment. Read More

    HLA class I expression predicts prognosis and therapeutic benefits from tyrosine kinase inhibitors in metastatic renal-cell carcinoma patients.
    Cancer Immunol Immunother 2017 Sep 16. Epub 2017 Sep 16.
    Department of Urology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Shanghai, 200032, China.
    Purpose: Classical HLA class I antigen is highly involved in antigen presentation and adaptive immune response against tumor. In this study, we explored its predictive value for treatment response and survival in metastatic renal-cell carcinoma (mRCC) patients.

    Experimental Design: A TKI cohort of 111 mRCC patients treated with sunitinib or sorafenib and a non-TKI cohort of 160 mRCC patients treated with interleukin-2 or interferon-α-based immunotherapy at a single institution were retrospectively enrolled. Read More

    Monitoring the response of urothelial precancerous lesions to Bacillus Calmette-Guerin at the proteome level in an in vivo rat model.
    Cancer Immunol Immunother 2017 Sep 15. Epub 2017 Sep 15.
    Department of Urology, Kocaeli University School of Medicine, Umuttepe Campus, 41380, Kocaeli, Turkey.
    Intravesical Bacillus Calmette-Guerin (BCG) is the best treatment modality for progression of non-muscle invasive bladder cancer. We aimed to monitor changes at the proteome level to identify putative protein biomarkers associated with the response of urothelial precancerous lesions to intravesical BCG treatment. The rats were divided into three groups (n = 10/group): control, non-treated, and BCG-treated groups. Read More

    Bile duct obstruction in a patient treated with nivolumab as second-line chemotherapy for advanced non-small-cell lung cancer: a case report.
    Cancer Immunol Immunother 2017 Sep 14. Epub 2017 Sep 14.
    Department of Gastroenterology, Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital, Honkomagome 3-18-22, Bunkyo, Tokyo, 113-8677, Japan.
    Immune checkpoint inhibitors (ICIs) are becoming a standard therapy for non-small-cell lung cancer in the advanced stage. As these ICIs become widely available in clinical practice, immune-related adverse effects will become more common. Here we report a patient with lung adenocarcinoma who was treated with nivolumab and developed obstruction because of biliary inflammation. Read More

    Administration of low-dose combination anti-CTLA4, anti-CD137, and anti-OX40 into murine tumor or proximal to the tumor draining lymph node induces systemic tumor regression.
    Cancer Immunol Immunother 2017 Sep 13. Epub 2017 Sep 13.
    Division of Oncology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
    The delivery of immunomodulators directly into the tumor potentially harnesses the existing antigen, tumor-specific infiltrating lymphocytes, and antigen presenting cells. This can confer specificity and generate a potent systemic anti-tumor immune response with lower doses and less toxicity compared to systemic administration, in effect an in situ vaccine. Here, we test this concept using the novel combination of immunomodulators anti-CTLA4, -CD137, and -OX40. Read More

    Tumor infiltrating lymphocytes in lymph node metastases of stage III melanoma correspond to response and survival in nine patients treated with ipilimumab at the time of stage IV disease.
    Cancer Immunol Immunother 2017 Sep 11. Epub 2017 Sep 11.
    Department of Dermatology/Allergology, Cantonal Hospital St. Gallen, Rorschacherstrasse 95, 9007, St. Gallen, Switzerland.
    Prognosis of metastatic melanoma improved with the development of checkpoint inhibitors. The role of tumor infiltrating lymphocytes (TILs) in lymph node metastases of stage III melanoma remains unclear. We retrospectively characterized TILs in primary melanomas and matched lymph node metastases (stage III melanoma) of patients treated with the checkpoint inhibitor ipilimumab. Read More

    Transcriptomic analysis of the tumor microenvironment to guide prognosis and immunotherapies.
    Cancer Immunol Immunother 2017 Sep 7. Epub 2017 Sep 7.
    INSERM, UMR_S 1138, Cordeliers Research Center, Team Cancer, Immune Control and Escape, 75006, Paris, France.
    Tumors are highly heterogeneous tissues where malignant cells are surrounded by and interact with a complex tumor microenvironment (TME), notably composed of a wide variety of immune cells, as well as vessels and fibroblasts. As the dialectical influence between tumor cells and their TME is known to be clinically crucial, we need tools that allow us to study the cellular composition of the microenvironment. In this focused research review, we report MCP-counter, a methodology based on transcriptomic markers that assesses the proportion of several immune and stromal cell populations in the TME from transcriptomic data, and we highlight how it can provide a way to decipher the complex mechanisms at play in tumors. Read More

    Clinical grade manufacturing of genetically modified, CAR-expressing NK-92 cells for the treatment of ErbB2-positive malignancies.
    Cancer Immunol Immunother 2017 Sep 6. Epub 2017 Sep 6.
    Institute for Transfusion Medicine, German Red Cross Blood Donation Service North-East, Blasewitzer Strasse 68/70, 01307, Dresden, Germany.
    Background: The NK-92/5.28.z cell line (also referred to as HER2. Read More

    The STAT3 inhibitor pyrimethamine displays anti-cancer and immune stimulatory effects in murine models of breast cancer.
    Cancer Immunol Immunother 2017 Sep 5. Epub 2017 Sep 5.
    Department of Immunology, Department of Surgery, Mayo Clinic, Guggenheim 3-42B, Rochester, MN, 55905, USA.
    The transcription factor signal activator and transducer or transcription (STAT3), which regulates genes controlling proliferation, survival, and invasion, is activated inappropriately in many human cancers, including breast cancer. Activation of STAT3 can lead to both malignant cellular behavior and suppression of immune cell function in the tumor microenvironment. Through a chemical-biology screen, pyrimethamine (PYR), an FDA approved anti-microbial drug, was identified as an inhibitor of STAT3 function at concentrations known to be achieved safely in humans. Read More

    Immune profiling of melanoma tumors reflecting aggressiveness in a preclinical model.
    Cancer Immunol Immunother 2017 Dec 4;66(12):1631-1642. Epub 2017 Sep 4.
    Cancer Immunology and Immunotherapy Center, "Saint Savas" Cancer Hospital, 171 Alexandras Avenue, 11522, Athens, Greece.
    Melanoma, like most solid tumors, is highly heterogeneous in terms of invasive, proliferative, and tumor-initiating potential. This heterogeneity is the outcome of differential gene expression resulting from conditions in the tumor microenvironment and the selective pressure of the immune system. To investigate possible signatures combining immune-related gene expression and lymphocyte infiltration, we established a preclinical model using B16. Read More

    Toll-like receptor 5 and 7 expression may impact prognosis of HPV-positive oropharyngeal squamous cell carcinoma patients.
    Cancer Immunol Immunother 2017 Dec 30;66(12):1619-1629. Epub 2017 Aug 30.
    Pathology, University of Helsinki, HUSLAB, and Helsinki University Hospital, P.O Box 21, 00014 University of Helsinki, Helsinki, Finland.
    A large subset of oropharyngeal squamous cell carcinomas (OPSCCs) is associated with HPV infection and has better outcome than non-viral-related tumors. Various malignancies also carry a role for TLRs, key activators of inflammation and innate immunity. We examined the expression of TLRs in OPSCC, and their association with HPV status and treatment outcome. Read More

    CTLA-4/CD80 pathway regulates T cell infiltration into pancreatic cancer.
    Cancer Immunol Immunother 2017 Dec 30;66(12):1609-1617. Epub 2017 Aug 30.
    Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA.
    The ability of some tumors to exclude effector T cells represents a major challenge to immunotherapy. T cell exclusion is particularly evident in pancreatic ductal adenocarcinoma (PDAC), a disease where blockade of the immune checkpoint molecule CTLA-4 has not produced significant clinical activity. In PDAC, effector T cells are often scarce within tumor tissue and confined to peritumoral lymph nodes and lymphoid aggregates. Read More

    Therapeutic antibodies against cancer stem cells: a promising approach.
    Cancer Immunol Immunother 2017 Nov 24;66(11):1383-1398. Epub 2017 Aug 24.
    Laboratory for Cancer Biology, Department of Medical Oncology and Clinical Research, Cancer Institute (WIA), 38, Sardar Patel Road, Chennai, Tamil Nadu, 600 036, India.
    Monoclonal antibodies have been extensively used to treat malignancy along with routine chemotherapeutic drugs. Chemotherapy for metastatic cancer has not been successful in securing long-term remission of disease. This is in part due to the resistance of cancer cells to drugs. Read More

    Interleukin 6 induces M2 macrophage differentiation by STAT3 activation that correlates with gastric cancer progression.
    Cancer Immunol Immunother 2017 Dec 21;66(12):1597-1608. Epub 2017 Aug 21.
    Department of General Surgery and Center of Minimal Invasive Gastrointestinal Surgery, Southwest Hospital, Third Military Medical University, No. 30 Gaotanyan Street, Chongqing, 400038, People's Republic of China.
    Interleukin 6 (IL-6) was abundant in the tumor microenvironment and played potential roles in tumor progression. In our study, the expression of IL-6 in tumor tissues from 36 gastric cancer (GC) patients was significantly higher than in non-tumor tissues. Moreover, the number of CD163(+)CD206(+) M2 macrophages that infiltrated in tumor tissues was significantly greater than those infiltrated in non-tumor tissues. Read More

    Regulatory T cell subsets in patients with medulloblastoma at diagnosis and during standard irradiation and chemotherapy (PBTC N-11).
    Cancer Immunol Immunother 2017 Dec 20;66(12):1589-1595. Epub 2017 Aug 20.
    The Preston A. Wells Center for Brain Tumor Therapy, McKnight Brain Institute, University of Florida, Room L1-183, Gainesville, FL, 32608, USA.
    Background: We evaluated circulating levels of immunosuppressive regulatory T cells (Tregs) and other lymphocyte subsets in patients with newly diagnosed medulloblastoma (MBL) undergoing surgery compared to a control cohort of patients undergo craniectomy for correction of Chiari malformation (CM) and further determined the impact of standard irradiation and chemotherapy on this cell population.

    Methods: Eligibility criteria for this biologic study included age 4-21 years, patients with CM undergoing craniectomy (as non-malignant surgical controls) and receiving dexamethasone for prevention of post-operative nausea, and those with newly diagnosed posterior fossa tumors (PFT) undergoing surgical resection and receiving dexamethasone as an anti-edema measure. Patients with confirmed MBL were also followed for longitudinal blood collection and analysis during radiotherapy and chemotherapy. Read More

    Novel prostate cancer immunotherapy with a DNA-encoded anti-prostate-specific membrane antigen monoclonal antibody.
    Cancer Immunol Immunother 2017 Dec 17;66(12):1577-1588. Epub 2017 Aug 17.
    Vaccine and Immunotherapy Center, The Wistar Institute, 3601 Spruce Street, Philadelphia, PA, 19104, USA.
    Prostate-specific membrane antigen (PSMA) is expressed at high levels on malignant prostate cells and is likely an important therapeutic target for the treatment of prostate carcinoma. Current immunotherapy approaches to target PSMA include peptide, cell, vector or DNA-based vaccines as well as passive administration of PSMA-specific monoclonal antibodies (mAb). Conventional mAb immunotherapy has numerous logistical and practical limitations, including high production costs and a requirement for frequent dosing due to short mAb serum half-life. Read More

    Mucosa-associated invariant T cells infiltrate hepatic metastases in patients with colorectal carcinoma but are rendered dysfunctional within and adjacent to tumor microenvironment.
    Cancer Immunol Immunother 2017 Dec 10;66(12):1563-1575. Epub 2017 Aug 10.
    Department of Microbiology and Immunology, Western University, 1151 Richmond Street, London, ON, N6A 5C1, Canada.
    Mucosa-associated invariant T (MAIT) cells are innate-like T lymphocytes that are unusually abundant in the human liver, a common site of colorectal carcinoma (CRC) metastasis. However, whether they contribute to immune surveillance against colorectal liver metastasis (CRLM) is essentially unexplored. In addition, whether MAIT cell functions can be impacted by chemotherapy is unclear. Read More

    Atopy and prostate cancer: Is there a link between circulating levels of IgE and PSA in humans?
    Cancer Immunol Immunother 2017 Dec 9;66(12):1557-1562. Epub 2017 Aug 9.
    Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Zurich, Switzerland.
    Background: Atopy has been investigated as a potential risk factor for prostate cancer. IgE antibodies may be major players in protective responses against tumours, through engendering antigen presentation and enhancing adaptive immune responses targeted towards a specific allergen, but potentially also against tumour-associated antigens such as prostate-specific antigen (PSA). We therefore cross-sectionally investigated associations between circulating levels of PSA and IgE in the National Health and Nutrition Examination Survey 2005-2006. Read More

    Evaluation of a xenogeneic vascular endothelial growth factor-2 vaccine in two preclinical metastatic tumor models in mice.
    Cancer Immunol Immunother 2017 Dec 3;66(12):1545-1555. Epub 2017 Aug 3.
    Laboratory of Gene Therapy, Department of Nutrition, Genetics and Ethology, Faculty of Veterinary Medicine, Ghent University, Heidestraat 19, 9820, Merelbeke, Belgium.
    In this study, a xenogeneic DNA vaccine encoding for human vascular endothelial growth factor receptor-2 (hVEGFR-2) was evaluated in two murine tumor models, the B16-F10 melanoma and the EO771 breast carcinoma model. The vaccine was administered by intradermal injection followed by electroporation. The immunogenicity and the biological efficacy of the vaccine were tested in (1) a prophylactic setting, (2) a therapeutic setting, and (3) a therapeutic setting combined with surgical removal of the primary tumor. Read More

    An unbiased in vivo functional genomics screening approach in mice identifies novel tumor cell-based regulators of immune rejection.
    Cancer Immunol Immunother 2017 Dec 2;66(12):1529-1544. Epub 2017 Aug 2.
    Department of Oncology and Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, 3970 Reservoir Road NW, Washington DC, 20057, USA.
    The clinical successes of immune checkpoint therapies for cancer make it important to identify mechanisms of resistance to anti-tumor immune responses. Numerous resistance mechanisms have been identified employing studies of single genes or pathways, thereby parsing the tumor microenvironment complexity into tractable pieces. However, this limits the potential for novel gene discovery to in vivo immune attack. Read More

    IL-4 blockade alters the tumor microenvironment and augments the response to cancer immunotherapy in a mouse model.
    Cancer Immunol Immunother 2017 Nov 21;66(11):1485-1496. Epub 2017 Jul 21.
    Department of Clinical Oncology, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan.
    Recent findings show that immune cells constitute a large fraction of the tumor microenvironment and that they modulate tumor progression. Clinical data indicate that chronic inflammation is present at tumor sites and that IL-4, in particular, is upregulated. Thus, we tested whether IL-4 neutralization would affect tumor immunity. Read More

    Role of regulatory T cells in acute myeloid leukemia patients undergoing relapse-preventive immunotherapy.
    Cancer Immunol Immunother 2017 Nov 18;66(11):1473-1484. Epub 2017 Jul 18.
    TIMM Laboratory, Sahlgrenska Cancer Center, University of Gothenburg, Medicinaregatan 1F, Box 425, 413 90, Gothenburg, Sweden.
    Regulatory T cells (Tregs) have been proposed to dampen functions of anti-neoplastic immune cells and thus promote cancer progression. In a phase IV trial (Re:Mission Trial, NCT01347996, http://www.clinicaltrials. Read More

    Oncolytic immunotherapy: unlocking the potential of viruses to help target cancer.
    Cancer Immunol Immunother 2017 Jul 15. Epub 2017 Jul 15.
    Columbia University Medical Center, New York, NY, USA.
    Oncolytic immunotherapy is a research area of cancer immunotherapy investigating the use of modified viruses to target cancer cells. A variety of different viral backbones (e.g. Read More

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