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    4498 results match your criteria Cancer immunology immunotherapy : CII[Journal]

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    Genetic variants in the HLA class II region associated with risk of cutaneous squamous cell carcinoma.
    Cancer Immunol Immunother 2018 May 12. Epub 2018 May 12.
    Department of Dermatology, Massachusetts General Hospital, 50 Staniford Street, Suite 270, 02114, Boston, MA, USA.
    Background: The immune system has been implicated in the pathophysiology of cutaneous squamous cell carcinoma (cSCC) as evidenced by the substantially increased risk of cSCC in immunosuppressed individuals. Associations between cSCC risk and single nucleotide polymorphisms (SNPs) in the HLA region have been identified by genome-wide association studies (GWAS). The translation of the associated HLA SNPs to structural amino acids changes in HLA molecules has not been previously elucidated. Read More

    Cystatin F as a regulator of immune cell cytotoxicity.
    Cancer Immunol Immunother 2018 May 10. Epub 2018 May 10.
    The Jane and Jerry Weintraub Center for Reconstructive Biotechnology, School of Dentistry, University of California-Los Angeles, Los Angeles, USA.
    Cysteine cathepsins are lysosomal peptidases involved in the regulation of innate and adaptive immune responses. Among the diverse processes, regulation of granule-dependent cytotoxicity of cytotoxic T-lymphocytes (CTLs) and natural killer (NK) cells during cancer progression has recently gained significant attention. The function of cysteine cathepsins is regulated by endogenous cysteine protease inhibitors-cystatins. Read More

    Myeloid-derived suppressor cells (MDSCs) in patients with solid tumors: considerations for granulocyte colony-stimulating factor treatment.
    Cancer Immunol Immunother 2018 May 10. Epub 2018 May 10.
    Department of Laboratory Medicine, Masaryk Memorial Cancer Institute, Zluty kopec 7, 656 53, Brno, Czech Republic.
    Myeloid-derived suppressor cells (MDSCs) have been shown to contribute to tumor escape from host immune surveillance and to cancer progression by production of tumor-promoting soluble factors. Granulocyte colony-stimulating factor (G-CSF) is a principle cytokine controlling granulocyte number. Recombinant human G-CSF (rhG-CSF) has become the main therapeutic agent for the treatment of neutropenia and prophylaxis of febrile neutropenia in cancer patients. Read More

    Author Correction: Hypericin-based photodynamic therapy induces surface exposure of damage-associated molecular patterns like HSP70 and calreticulin.
    Cancer Immunol Immunother 2018 May 8. Epub 2018 May 8.
    Cell Death Research and Therapy Unit, Department of Molecular Cell Biology, Faculty of Medicine, Catholic University of Leuven, Campus Gasthuisberg O&N1, Herestraat 49, 3000, Leuven, Belgium.
    This correction refers to our Short Communication published in Cancer Immunology Immunotherapy in the year 2012 [1]. It has come to our attention that some errors resulting from accidental oversight concerning incorrect deletion/replacement of temporary placeholder images during figure assembly and mounting occurred during the assembly of the "Intracellular Proteins" immunoblots presented in Fig. 1A and Fig. Read More

    VISTA expression on tumor-infiltrating inflammatory cells in primary cutaneous melanoma correlates with poor disease-specific survival.
    Cancer Immunol Immunother 2018 May 8. Epub 2018 May 8.
    Roswell Park Cancer Institute, University of Buffalo, The State University of New York, Elm and Carlton, Buffalo, NY, 14263, USA.
    Adaptive immune responses contribute to the pathogenesis of melanoma by facilitating immune evasion. V-domain Ig suppressor of T-cell activation (VISTA) is a potent negative regulator of T-cell function and is expressed at high levels on monocytes, granulocytes, and macrophages, and at lower densities on T-cell populations within the tumor microenvironment. In this study, 85 primary melanoma specimens were selected from pathology tissue archives and immunohistochemically stained for CD3, PD-1, PD-L1, and VISTA. Read More

    Pushing the limits of immune-related response: a case of "extreme pseudoprogression".
    Cancer Immunol Immunother 2018 May 4. Epub 2018 May 4.
    Department of Medicine, National University Health System, Singapore, Singapore.
    The advent of immune checkpoint targeted immunotherapy has seen a spectrum of immune-related phenomena in both tumor responses and toxicities. We describe a case of pseudoprogression that pushes the limits of immune-related response criteria and challenges the boundaries and definitions set by trial protocols. A middle-aged man with conventional clear cell renal cell carcinoma (RCC) had received multiple prior systemic treatments including vascular endothelial growth factor receptor tyrosine kinase inhibitors, as well as multiple surgeries and radiotherapy treatments. Read More

    Role of MDA5 and interferon-I in dendritic cells for T cell expansion by anti-tumor peptide vaccines in mice.
    Cancer Immunol Immunother 2018 Apr 25. Epub 2018 Apr 25.
    Cancer Immunology, Immunotherapy and Tolerance Program, Georgia Cancer Center, Augusta University, 1410 Laney Walker Blvd., CN-4121, Augusta, GA, 30912, USA.
    Cytotoxic T lymphocytes (CTLs) are effective components of the immune system capable of destroying tumor cells. Generation of CTLs using peptide vaccines is a practical approach to treat cancer. We have previously described a peptide vaccination strategy that generates vast numbers of endogenous tumor-reactive CTLs after two sequential immunizations (prime-boost) using poly-ICLC adjuvant, which stimulates endosomal toll-like receptor 3 (TLR3) and cytoplasmic melanoma differentiation antigen 5 (MDA5). Read More

    The binding of an anti-PD-1 antibody to FcγRΙ has a profound impact on its biological functions.
    Cancer Immunol Immunother 2018 Apr 23. Epub 2018 Apr 23.
    BeiGene (Beijing) Co., Ltd., No. 30 Science Park Road, Zhong-Guan-Cun Life Science Park, Changping District, Beijing, 102206, People's Republic of China.
    Antibodies targeting PD-1 have been demonstrated durable anti-cancer activity in certain cancer types. However, the anti-PD-1 antibodies are less or not efficacious in many situations, which might be attributed to co-expression of multiple inhibitory receptors or presence of immunosuppressive cells in the tumor microenvironment. Most of the anti-PD-1 antibodies used in clinical studies are of IgG4 isotype with the S228P mutation (IgG4). Read More

    Regulatory T cells control endothelial chemokine production and migration of T cells into intestinal tumors of APC mice.
    Cancer Immunol Immunother 2018 Apr 18. Epub 2018 Apr 18.
    Department of Microbiology and Immunology, Institute of Biomedicine, The Sahlgrenska Academy, University of Gothenburg, Box 435, 405 30, Gothenburg, Sweden.
    Tumor-infiltrating lymphocytes are crucial for anti-tumor immunity. We have previously shown that regulatory T cells (Treg) are able to reduce T-cell transendothelial migration in vitro and accumulation of effector T cells in intestinal tumors in vivo. Treg depletion also resulted in increased levels of the chemokines CXCL9 and CXCL10 specifically in the tumors. Read More

    Personalized cancer vaccines: adjuvants are important, too.
    Cancer Immunol Immunother 2018 Apr 11. Epub 2018 Apr 11.
    Department of Immunology, Interfaculty Institute for Cell Biology, Eberhard Karls University and German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ) Partner Site Tübingen, Auf der Morgenstelle 15, 72076, Tübingen, Germany.
    Therapeutic cancer vaccines have shown limited clinical efficacy so far. Nevertheless, in the meantime, our understanding of immune cell function and the interactions of immune cells with growing tumors has advanced considerably. We are now in a position to invest this knowledge into the design of more powerful vaccines and therapy combinations aimed at increasing immunogenicity and decreasing tumor-induced immunosuppression. Read More

    Induction of a central memory and stem cell memory phenotype in functionally active CD4 and CD8 CAR T cells produced in an automated good manufacturing practice system for the treatment of CD19 acute lymphoblastic leukemia.
    Cancer Immunol Immunother 2018 Mar 31. Epub 2018 Mar 31.
    Department of Pediatric Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, Dr. von Hauner University Children's Hospital, Ludwig Maximilian University Munich, Lindwurmstrasse 4, 80337, Munich, Germany.
    Relapsed/refractory B-precursor acute lymphoblastic leukemia (pre-B ALL) remains a major therapeutic challenge. Chimeric antigen receptor (CAR) T cells are promising treatment options. Central memory T cells (Tcm) and stem cell-like memory T cells (Tscm) are known to promote sustained proliferation and persistence after T-cell therapy, constituting essential preconditions for treatment efficacy. Read More

    Tumor lysate-based vaccines: on the road to immunotherapy for gallbladder cancer.
    Cancer Immunol Immunother 2018 Mar 29. Epub 2018 Mar 29.
    Disciplinary Program of Immunology, Institute of Biomedical Sciences, Faculty of Medicine, Universidad de Chile, Independencia 1027, building H, Third floor, 8380453, Santiago, Chile.
    Immunotherapy based on checkpoint blockers has proven survival benefits in patients with melanoma and other malignancies. Nevertheless, a significant proportion of treated patients remains refractory, suggesting that in combination with active immunizations, such as cancer vaccines, they could be helpful to improve response rates. During the last decade, we have used dendritic cell (DC) based vaccines where DCs loaded with an allogeneic heat-conditioned melanoma cell lysate were tested in a series of clinical trials. Read More

    Depleted polymorphonuclear leukocytes in human metastatic liver reflect an altered immune microenvironment associated with recurrent metastasis.
    Cancer Immunol Immunother 2018 Mar 23. Epub 2018 Mar 23.
    School of Biochemistry and Immunology and School of Medicine, Trinity Biomedical Sciences Institute, Trinity College Dublin, 154-160 Pearse Street, Dublin 2, D02 R590, Ireland.
    Background: Hepatic immunity, normally protective against neoplasia, is subverted in colorectal liver metastasis (CRLM). Here, we compare the inflammatory microenvironment of CRLM-bearing liver tissue to donor liver.

    Methods: Twenty-five patients undergoing resection for CRLM were recruited, 13 of whom developed intrahepatic recurrence within 18 months. Read More

    Diacylglycerol kinase α inactivation is an integral component of the costimulatory pathway that amplifies TCR signals.
    Cancer Immunol Immunother 2018 Jun 23;67(6):965-980. Epub 2018 Mar 23.
    Department of Immunology and Oncology, Centro Nacional de Biotecnología (CNB-CSIC), Darwin 3, UAM Campus de Cantoblanco, 28049, Madrid, Spain.
    The arsenal of cancer therapies has evolved to target T lymphocytes and restore their capacity to destroy tumor cells. T cells rely on diacylglycerol (DAG) to carry out their functions. DAG availability and signaling are regulated by the enzymes diacylglycerol kinase (DGK) α and ζ, whose excess function drives T cells into hyporesponsive states. Read More

    Quantitative T-cell repertoire analysis of peripheral blood mononuclear cells from lung cancer patients following long-term cancer peptide vaccination.
    Cancer Immunol Immunother 2018 Jun 22;67(6):949-964. Epub 2018 Mar 22.
    Department of Chest Surgery, School of Medicine, Fukushima Medical University, Fukushima, 960-1295, Japan.
    Therapeutic cancer peptide vaccination is an immunotherapy designed to elicit cytotoxic T-lymphocyte (CTL) responses in patients. A number of therapeutic vaccination trials have been performed, nevertheless there are only a few reports that have analyzed the T-cell receptors (TCRs) expressed on tumor antigen-specific CTLs. Here, we use next-generation sequencing (NGS) to analyze TCRs of vaccine-induced CTL clones and the TCR repertoire of bulk T cells in peripheral blood mononuclear cells (PBMCs) from two lung cancer patients over the course of long-term vaccine therapy. Read More

    The novel deubiquitinase inhibitor b-AP15 induces direct and NK cell-mediated antitumor effects in human mantle cell lymphoma.
    Cancer Immunol Immunother 2018 Jun 19;67(6):935-947. Epub 2018 Mar 19.
    Clinical Collaboration Unit Translational Immunology, German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Partner site Tübingen, Otfried-Müller-Str. 10, 72076, Tübingen, Germany.
    The first therapeutic proteasome inhibitor bortezomib has clinical efficacy in mantle cell lymphoma (MCL) which resulted in its incorporation in treatment algorithms for this disease. Impairment of proteasomal function by bortezomib is mediated via inhibition of the 20S core particle. However, proteasome function can also be modified by targeting upstream components of the ubiquitin-proteasome system. Read More

    Enhanced expression of PD-1 and other activation markers by CD4+ T cells of young but not old patients with metastatic melanoma.
    Cancer Immunol Immunother 2018 Jun 15;67(6):925-933. Epub 2018 Mar 15.
    Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9700 RB, Groningen, The Netherlands.
    The biological behavior of melanoma is unfavorable in the elderly when compared to young subjects. We hypothesized that differences in T-cell responses might underlie the distinct behavior of melanoma in young and old melanoma patients. Therefore, we investigated the circulating T-cell compartment of 34 patients with metastatic melanoma and 42 controls, which were classified as either young or old. Read More

    Quantifying tumor-infiltrating immune cells from transcriptomics data.
    Cancer Immunol Immunother 2018 Mar 14. Epub 2018 Mar 14.
    Biocenter, Division for Bioinformatics, Medical University of Innsbruck, Innrain 80, 6020, Innsbruck, Austria.
    By exerting pro- and anti-tumorigenic actions, tumor-infiltrating immune cells can profoundly influence tumor progression, as well as the success of anti-cancer therapies. Therefore, the quantification of tumor-infiltrating immune cells holds the promise to unveil the multi-faceted role of the immune system in human cancers and its involvement in tumor escape mechanisms and response to therapy. Tumor-infiltrating immune cells can be quantified from RNA sequencing data of human tumors using bioinformatics approaches. Read More

    Cancer immunotherapy in patients with brain metastases.
    Cancer Immunol Immunother 2018 May 8;67(5):703-711. Epub 2018 Mar 8.
    Center for Cancer Immune Therapy (CCIT), Department of Hematology, Herlev Hospital, University of Copenhagen, Herlev Ringvej 75, 2730, Herlev, Denmark.
    The exclusion of "real-world" patients from registration clinical trials of cancer immunotherapy represents a significant emerging issue. For instance, a large fraction of cancer patients develops brain metastases during the course of the disease, but results from large prospective clinical trials investigating this considerable proportion of the cancer patient population are currently lacking. To provide a useful tool for the clinician in a "real-world" setting, we have reviewed the available literature regarding the safety and efficacy of immune check-point inhibitors in patients with cancer metastatic to the brain. Read More

    Rituximab as a therapeutic option for patients with advanced melanoma.
    Cancer Immunol Immunother 2018 Jun 7;67(6):917-924. Epub 2018 Mar 7.
    Department of Dermatology and National Center for Tumor Diseases, University Hospital Heidelberg, Im Neuenheimer Feld 460, 69120, Heidelberg, Germany.
    Treatment of metastatic melanoma remains challenging, despite a variety of new and promising immunotherapeutic and targeted approaches to therapy. New treatment options are still needed to improve long-term tumour control. We present a case series of seven patients with metastatic melanoma who were treated individually with the anti-CD20 antibody rituximab between July 2014 and July 2015. Read More

    The non-small cell lung cancer immune landscape: emerging complexity, prognostic relevance and prospective significance in the context of immunotherapy.
    Cancer Immunol Immunother 2018 Jun 7;67(6):1011-1022. Epub 2018 Mar 7.
    Department of Research, Human Tumors Immunobiology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, 20133, Milan, Italy.
    Immunotherapy of non-small cell lung cancer (NSCLC), by immune checkpoint inhibitors, has profoundly improved the clinical management of advanced disease. However, only a fraction of patients respond and no effective predictive factors have been defined. Here, we discuss the prospects for identification of such predictors of response to immunotherapy, by fostering an in-depth analysis of the immune landscape of NSCLC. Read More

    Rational combinations of in vivo cancer antigen priming and adoptive T-cell therapy mobilize immune and clinical responses in terminal cancers.
    Cancer Immunol Immunother 2018 Jun 6;67(6):907-915. Epub 2018 Mar 6.
    Xiamen Key Laboratory for Translational Medicine of Cancer Theranostics, School of Pharmaceutical Sciences, Xiamen University, #246-248, Xiangan Nanlu, Xiangan District, Xiamen, China.
    Purpose: It is now recognized that solid tumors encroach on the host's immune microenvironment to favor its own proliferation. Strategies to enhance the specificity of the endogenous T-cell population against tumors have been met with limited clinical success. We aimed to devise a two-tier protocol coupling in vivo whole antigen priming with ex vivo cellular expansion to clinically evaluate survival in patients following re-infusion of primed, autologous T cells, thereby determining treatment efficacy. Read More

    CD137L dendritic cells induce potent response against cancer-associated viruses and polarize human CD8 T cells to Tc1 phenotype.
    Cancer Immunol Immunother 2018 Jun 5;67(6):893-905. Epub 2018 Mar 5.
    Department of Physiology and Immunology Programme, National University of Singapore (NUS), 2 Medical Dr., Singapore, 117593, Singapore.
    Therapeutic tumor vaccination based on dendritic cells (DC) is safe; however, its efficacy is low. Among the reasons for only a subset of patients benefitting from DC-based immunotherapy is an insufficient potency of in vitro generated classical DCs (cDCs), made by treating monocytes with GM-CSF + IL-4 + maturation factors. Recent studies demonstrated that CD137L (4-1BBL, TNFSF9) signaling differentiates human monocytes to a highly potent novel type of DC (CD137L-DCs) which have an inflammatory phenotype and are closely related to in vivo DCs. Read More

    T-cell receptor-β V and J usage, in combination with particular HLA class I and class II alleles, correlates with cancer survival patterns.
    Cancer Immunol Immunother 2018 Jun 5;67(6):885-892. Epub 2018 Mar 5.
    Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, 12901 Bruce B. Downs Bd. MDC7, Tampa, FL, 33612, USA.
    Class I and class II HLA proteins, respectively, have been associated with subsets of V(D)J usage resulting from recombination of the T-cell receptor (TCR) genes. Additionally, particular HLA alleles, in combination with dominant TCR V(D)J recombinations, have been associated with several autoimmune diseases. The recovery of TCR recombination reads from tumor specimen exome files has allowed rapid and extensive assessments of V(D)J usage, likely for cancer resident T-cells, across relatively large cancer datasets. Read More

    Tumor-associated myeloid cells promote tumorigenesis of non-tumorigenic human and murine prostatic epithelial cell lines.
    Cancer Immunol Immunother 2018 Jun 3;67(6):873-883. Epub 2018 Mar 3.
    Department of Immunology, Roswell Park Cancer Institute, Elm and Carlton Sts, Buffalo, NY, 14263, USA.
    The etiology of prostate cancer is poorly understood, but it is a multi-step process that has been linked to environmental factors that induce inflammation within the gland. Glands of prostate cancer patients frequently contain multiple zones of disease at various stages of progression. The factors that drive disease progression from an indolent benign stage to aggressive disease are not well-defined. Read More

    Daratumumab augments alloreactive natural killer cell cytotoxicity towards CD38+ multiple myeloma cell lines in a biochemical context mimicking tumour microenvironment conditions.
    Cancer Immunol Immunother 2018 Jun 2;67(6):861-872. Epub 2018 Mar 2.
    Department of Transplantation Immunology, Tissue Typing Laboratory, Maastricht University Medical Center+, P.O. Box 5800, 6202 AZ, Maastricht, The Netherlands.
    Natural killer (NK) cell-based immunotherapy is a promising novel approach to treat cancer. However, NK cell function has been shown to be potentially diminished by factors common in the tumor microenvironment (TME). In this study, we assessed the synergistic potential of antibody-dependent cell-mediated cytotoxicity (ADCC) and killer immunoglobin-like receptor (KIR)-ligand mismatched NK cells to potentiate NK cell antitumor reactivity in multiple myeloma (MM). Read More

    Impaired lymphocyte function in patients with hepatic malignancies after selective internal radiotherapy.
    Cancer Immunol Immunother 2018 May 2;67(5):843-853. Epub 2018 Mar 2.
    Institute for Transfusion Medicine, University Hospital Essen, Virchowstraße 179, 45147, Essen, Germany.
    The purpose of our study was to assess the immune function of patients with inoperable hepatic malignancies after treatment with selective internal radiotherapy (SIRT) and to identify possible correlations with clinical parameters. In 25 patients receiving SIRT lymphocyte proliferation and the production of pro- and anti-inflammatory cytokines (interferon-γ and interleukin-10) after stimulation with mitogens and microbial antigens were tested prior to therapy, directly after therapy (day 1) and at day 2, 7 and 28 post therapy using the lymphocyte transformation test and enzyme-linked immunospot assays. Absolute counts and percentages of leukocyte and lymphocyte subsets were determined by flow cytometry. Read More

    Early detection of hepatocellular carcinoma using autoantibody profiles from a panel of tumor-associated antigens.
    Cancer Immunol Immunother 2018 May 1;67(5):835-841. Epub 2018 Mar 1.
    Department of Molecular and Experimental Medicine, MEM290, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037, USA.
    Background: Multiple antigen miniarrays used for detecting autoantibodies to tumor-associated antigens (TAAs) can be a useful approach for cancer detection and diagnosis. We here address a very specific question: might there be autoimmune responses to TAAs which precede clinical detection of hepatocellular carcinoma (HCC) in HBV and HCV chronic liver disease patients under continuous medical surveillance, and if so, could these anti-TAAs be added to the armamentarium of diagnostic tests?

    Methods: We here examine the utility of a panel of 12 TAAs for the diagnosis of hepatocellular carcinoma (HCC). We derived a predictive rule for the presence of HCC based on the panel, from a cohort comprising 160 HCC patients and 90 normals. Read More

    Ipilimumab in metastatic melanoma patients with pre-existing autoimmune disorders.
    Cancer Immunol Immunother 2018 May 27;67(5):825-834. Epub 2018 Feb 27.
    Department of Dermatology and Allergy, Skin Cancer Center Hannover, Hannover Medical School, Hanover, Germany.
    Background: Ipilimumab and programmed death (PD) 1-antibodies are effective treatment options in metastatic melanoma. The safety and efficacy of ipilimumab in patients with pre-existing autoimmune disorders (AD) has only been evaluated in a selected number of patients.

    Methods: We performed a retrospective analysis in 14 German skin cancer centers for patients with metastatic melanoma and pre-existing AD treated with ipilimumab. Read More

    The multi-receptor inhibitor axitinib reverses tumor-induced immunosuppression and potentiates treatment with immune-modulatory antibodies in preclinical murine models.
    Cancer Immunol Immunother 2018 May 27;67(5):815-824. Epub 2018 Feb 27.
    Laboratory of Cancer Immunology, Department of Biomedicine, University Hospital and University of Basel, Hebelstr. 20, 4031, Basel, Switzerland.
    Cancer immunotherapies have significantly improved the prognosis of cancer patients. Despite the clinical success of targeting inhibitory checkpoint receptors, including PD-1 and/or CTLA-4 on T cells, only a minority of patients derive benefit from these therapies. New strategies to improve cancer immunotherapy are therefore needed. Read More

    Defective HLA class I antigen processing machinery in cancer.
    Cancer Immunol Immunother 2018 Jun 27;67(6):999-1009. Epub 2018 Feb 27.
    Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02114, USA.
    Malignant transformation of cells is frequently associated with defective HLA class I antigen processing machinery (APM) component expression. This abnormality may have functional relevance, since it may have a negative impact on tumor cell recognition by cognate T cells. Furthermore, HLA class I APM abnormalities appear to have clinical significance, since they are associated with poor prognosis in several malignant diseases and may play a role in the resistance to immune checkpoint inhibitor-based immunotherapy. Read More

    PD-L1, B7-H3, and PD-1 expression in immunocompetent vs. immunosuppressed patients with cutaneous squamous cell carcinoma.
    Cancer Immunol Immunother 2018 May 27;67(5):805-814. Epub 2018 Feb 27.
    University of Maryland Greenebaum Comprehensive Cancer Center, 22 South Greene Street Room N9E29, Baltimore, MD, 21201, USA.
    Background: To characterize the expression of co-signaling molecules PD-L1, PD-1, and B7-H3 in cutaneous squamous cell carcinoma (cSCC) by immune status.

    Methods: We retrospectively analyzed 66 cases of cSCC treated with surgical resection from 2012 to 2015. Immunostained tumor sections were analyzed for percent of tumor cells expressing PD-L1 (Tum-PD-L1%), B7-H3 (Tum-B7-H3%), density of peri and intratumoral CD8 T cells (CD8 density), proportion of CD8 T cells expressing PD-1 (CD8-PD-1%) and of tumor-infiltrating immune cells (TII) expressing PD-L1 (TII-PD-L1%). Read More

    Certain BCG-reactive responses are associated with bladder cancer prognosis.
    Cancer Immunol Immunother 2018 May 24;67(5):797-803. Epub 2018 Feb 24.
    Departments of Urology II, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, Hubei, China.
    A subset of bladder patients does not respond to BCG treatment effectively and the underlying reason behind this observation is currently unclear. CD4 T cells are composed of various subsets that each expresses a distinctive set of cytokines and can potently shift the immune response toward various directions. In this study, we examined the CD4 T-cell cytokine response in bladder cancer patients toward BCG stimulation. Read More

    Mucosa-associated invariant T cells in malignancies: a faithful friend or formidable foe?
    Cancer Immunol Immunother 2018 Feb 22. Epub 2018 Feb 22.
    Department of Microbiology and Immunology, Western University, 1151 Richmond Street, London, ON, N6A 5C1, Canada.
    Mucosa-associated invariant T (MAIT) cells are a subset of innate-like T lymphocytes known for their ability to respond to MHC-related protein 1 (MR1)-restricted stimuli and select cytokine signals. They are abundant in humans and especially enriched in mucosal layers, common sites of neoplastic transformation. MAIT cells have been found within primary and metastatic tumors. Read More

    Antitumor in situ vaccination effect of TNFα and IL-12 plasmid DNA electrotransfer in a murine melanoma model.
    Cancer Immunol Immunother 2018 May 21;67(5):785-795. Epub 2018 Feb 21.
    Department of Experimental Oncology, Institute of Oncology Ljubljana, Zaloska 2, 1000, Ljubljana, Slovenia.
    Gene electrotransfer (GET) is one of the most efficient non-viral gene therapy approaches for the localized transfer of multiple genes into tumors in vivo; therefore, it is especially promising for delivering different cytokines that are toxic if administered systemically. In this study, we used concomitant intratumoral GET of two cytokines: tumor necrosis factor alpha (TNFα), a potent cytotoxic cytokine to induce in situ vaccination, and interleukin 12 (IL-12), an immunostimulatory cytokine to boost the primed local immune response into a systemic one. After performing GET in murine melanoma tumors, both TNFα and IL-12 mRNA levels were significantly increased, which resulted in a pronounced delay in tumor growth of 27 days and a prolonged survival time of mice. Read More

    The BCR-ABL inhibitor nilotinib influences phenotype and function of monocyte-derived human dendritic cells.
    Cancer Immunol Immunother 2018 May 21;67(5):775-783. Epub 2018 Feb 21.
    Department of Medical Oncology, Hematology, Immunology, Rheumatology and Pulmology, University Hospital Tübingen, Otfried-Müller-Straße 10, 72076, Tübingen, Germany.
    In chronic myeloid leukemia (CML), the translocation t(9;22) results in the fusion protein BCR-ABL (breakpoint cluster region-abelson murine leukemia), a tyrosine kinase mediating oncogenic signaling which is successfully targeted by treatment with BCR-ABL inhibitors like imatinib. However, BCR-ABL inhibitors may also affect antitumor immunity. For instance, it was reported that imatinib impairs the function of dendritic cells (DCs) that play a central role in initiating and sustaining T cell responses. Read More

    TriCurin, a synergistic formulation of curcumin, resveratrol, and epicatechin gallate, repolarizes tumor-associated macrophages and triggers an immune response to cause suppression of HPV+ tumors.
    Cancer Immunol Immunother 2018 May 16;67(5):761-774. Epub 2018 Feb 16.
    Department of Chemistry, Building 6S, The City University of New York at The College of Staten Island, 2800 Victory Boulevard, Staten Island, NY, 10314, USA.
    Our earlier studies reported a unique potentiated combination (TriCurin) of curcumin (C) with two other polyphenols. The TriCurin-associated C displays an IC50 in the low micromolar range for cultured HPV+ TC-1 cells. In contrast, because of rapid degradation in vivo, the TriCurin-associated C reaches only low nano-molar concentrations in the plasma, which are sub-lethal to tumor cells. Read More

    Chimeric antigen receptors with human scFvs preferentially induce T cell anti-tumor activity against tumors with high B7H6 expression.
    Cancer Immunol Immunother 2018 May 16;67(5):749-759. Epub 2018 Feb 16.
    Department of Microbiology and Immunology, The Geisel School of Medicine at Dartmouth, One Medical Center Drive, Lebanon, NH, 03756, USA.
    B7H6 is emerging as a promising tumor antigen that is known to be expressed on a wide array of tumors and is reported to stimulate anti-tumor responses from the immune system. As such, B7H6 presents a good target for tumor-specific immunotherapies. B7H6-specific chimeric antigen receptors (CAR) based on a murine antibody showed successful targeting and elimination of tumors expressing B7H6. Read More

    Chronic lymphocytic leukemia cells acquire regulatory B-cell properties in response to TLR9 and CD40 activation.
    Cancer Immunol Immunother 2018 May 15;67(5):739-748. Epub 2018 Feb 15.
    Department of Hematology and Bone Marrow Transplantation, Rambam Health Care Campus, 8, Ha'Aliya Street, 3109601, Haifa, Israel.
    Circulating chronic lymphocytic leukemia (CLL) cells share phenotypic features with certain subsets of regulatory B-cells (Bregs). The latter cells have been reported to negatively regulate immune cell responses, mostly by provision of IL-10. The purpose of the current study was to identify and delineate Breg properties of CLL cells. Read More

    Identification of tumor-reactive B cells and systemic IgG in breast cancer based on clonal frequency in the sentinel lymph node.
    Cancer Immunol Immunother 2018 May 9;67(5):729-738. Epub 2018 Feb 9.
    Department of Surgery, Vermont Cancer Center, University of Vermont Larner College of Medicine, 89 Beaumont Avenue, Given Medical Building, Burlington, VT, 05405, USA.
    A better understanding of antitumor immune responses is the key to advancing the field of cancer immunotherapy. Endogenous immunity in cancer patients, such as circulating anticancer antibodies or tumor-reactive B cells, has been historically yet incompletely described. Here, we demonstrate that tumor-draining (sentinel) lymph node (SN) is a rich source for tumor-reactive B cells that give rise to systemic IgG anticancer antibodies circulating in the bloodstream of breast cancer patients. Read More

    Pretreatment neutrophil-to-lymphocyte ratio is associated with outcome of advanced-stage cancer patients treated with immunotherapy: a meta-analysis.
    Cancer Immunol Immunother 2018 May 8;67(5):713-727. Epub 2018 Feb 8.
    Department of Medical Oncology, Shanghai Pulmonary Hospital, Thoracic Cancer Institute, Tongji University School of Medicine, No. 507, Zheng Min Road, Shanghai, 200433, People's Republic of China.
    Background: To investigate the association between pretreatment blood neutrophil-to-lymphocyte ratio (NLR) and clinical outcomes for advanced-stage cancer patients treated with immunotherapy.

    Methods: We conducted a comprehensive literature search to assess the relationship between pretreatment blood NLR and overall survival (OS) or progression-free survival (PFS) in advanced-stage cancer patients treated with immunotherapy. Published data including hazard ratios (HRs) and related 95% confidence interval (CI) were extracted. Read More

    N-acetyl cysteine protects anti-melanoma cytotoxic T cells from exhaustion induced by rapid expansion via the downmodulation of Foxo1 in an Akt-dependent manner.
    Cancer Immunol Immunother 2018 Apr 2;67(4):691-702. Epub 2018 Feb 2.
    Department of Microbiology and Immunology, Medical University of South Carolina, MSC 250504, 173 Ashley Avenue, Charleston, SC, 29425, USA.
    Therapeutic outcomes for adoptive cell transfer (ACT) therapy are constrained by the quality of the infused T cells. The rapid expansion necessary to obtain large numbers of cells results in a more terminally differentiated phenotype with decreased durability and functionality. N-acetyl cysteine (NAC) protects against activation-induced cell death (AICD) and improves anti-tumor efficacy of Pmel-1 T cells in vivo. Read More

    An IL-15 superagonist/IL-15Rα fusion complex protects and rescues NK cell-cytotoxic function from TGF-β1-mediated immunosuppression.
    Cancer Immunol Immunother 2018 Apr 1;67(4):675-689. Epub 2018 Feb 1.
    Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 10 Center Drive, Room 8B13, Bethesda, MD, 20892, USA.
    Natural killer (NK) cells are innate cytotoxic lymphocytes that play a fundamental role in the immunosurveillance of cancers. NK cells of cancer patients exhibit impaired function mediated by immunosuppressive factors released from the tumor microenvironment (TME), such as transforming growth factor (TGF)-β1. An interleukin (IL)-15 superagonist/IL-15 receptor α fusion complex (IL-15SA/IL-15RA; ALT-803) activates the IL-15 receptor on CD8 T cells and NK cells, and has shown significant anti-tumor activity in several in vivo studies. Read More

    Clinical translation and regulatory aspects of CAR/TCR-based adoptive cell therapies-the German Cancer Consortium approach.
    Cancer Immunol Immunother 2018 Apr 29;67(4):513-523. Epub 2018 Jan 29.
    Paul-Ehrlich-Institut (PEI, German Federal Institute for Vaccines and Biomedicines), Langen, Germany.
    Adoptive transfer of T cells genetically modified by TCRs or CARs represents a highly attractive novel therapeutic strategy to treat malignant diseases. Various approaches for the development of such gene therapy medicinal products (GTMPs) have been initiated by scientists in recent years. To date, however, the number of clinical trials commenced in Germany and Europe is still low. Read More

    Epstein-Barr virus strain heterogeneity impairs human T-cell immunity.
    Cancer Immunol Immunother 2018 Apr 27;67(4):663-674. Epub 2018 Jan 27.
    Children's Hospital, Technische Universität München, Munich, Germany.
    The Epstein-Barr virus (EBV) establishes lifelong infections in > 90% of the human population. Although contained as asymptomatic infection by the immune system in most individuals, EBV is associated with the pathogenesis of approximately 1.5% of all cancers in humans. Read More

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