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    4396 results match your criteria Cancer immunology immunotherapy : CII[Journal]

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    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 Sep 4. 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 Aug 30. 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 Aug 30. 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 Aug 24. 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 Aug 21. 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 Aug 20. 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 Aug 17. 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 Aug 10. 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 Aug 9. 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 Aug 3. 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 Aug 2. 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 Jul 21. 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 Jul 18. 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

    Cerebellar degeneration-related proteins 2 and 2-like are present in ovarian cancer in patients with and without Yo antibodies.
    Cancer Immunol Immunother 2017 Jul 14. Epub 2017 Jul 14.
    Department of Clinical Medicine, University of Bergen, Jonas Lies veg 87, 5021, Bergen, Norway.
    Background: Cerebellar degeneration-related protein 2 (CDR2) has been presumed to be the main antigen for the onconeural antibody Yo, which is strongly associated with ovarian cancer and paraneoplastic cerebellar degeneration (PCD). Recent data show that Yo antibodies also target the CDR2-like protein (CDR2L). We, therefore, examined the expression of CDR2 and CDR2L in ovarian cancer tissue from patients with and without Yo antibodies and from various other cancerous and normal human tissues. Read More

    CTLA-4 expression in the non-small cell lung cancer patient tumor microenvironment: diverging prognostic impact in primary tumors and lymph node metastases.
    Cancer Immunol Immunother 2017 Jul 13. Epub 2017 Jul 13.
    Department of Oncology, University Hospital of North Norway, Mailbox 13, 9038, Tromso, Norway.
    The immune checkpoint receptor CTLA-4 plays a crucial part in negatively regulating T cell activation and maintaining self-tolerance. It is frequently overexpressed in a variety of malignancies, yet its prognostic impact in non-small cell lung cancer (NSCLC) remains unclear. We constructed tissue microarrays from tumor tissue samples and evaluated the immunohistochemical expression of CTLA-4 in 536 patients with primary resected stage I-IIIA NSCLC. Read More

    Regulatory myeloid cells: an underexplored continent in B-cell lymphomas.
    Cancer Immunol Immunother 2017 Aug 8;66(8):1103-1111. Epub 2017 Jul 8.
    CHU de Rennes, Pole de Biologie, Rennes, France.
    In lymphomas arising from the germinal center, prognostic factors are linked to the myeloid compartment. In particular, high circulating monocyte or myeloid-derived suppressor cell counts are associated with poor prognosis for patients with high-grade B-cell lymphomas. Macrophages with an M2 phenotype are enriched within lymphoma tumors. Read More

    Circulating myeloid-derived suppressor cells increase in patients undergoing neo-adjuvant chemotherapy for breast cancer.
    Cancer Immunol Immunother 2017 Jul 7. Epub 2017 Jul 7.
    Division of Surgical Oncology, Department of Surgery, The Ohio State University, 410 W 10th Ave, N911 Doan Hall, Columbus, OH, 43210-1267, USA.
    This study sought to evaluate whether myeloid-derived suppressor cells (MDSC) could be affected by chemotherapy and correlate with pathologic complete response (pCR) in breast cancer patients receiving neo-adjuvant chemotherapy. Peripheral blood levels of granulocytic (G-MDSC) and monocytic (M-MDSC) MDSC were measured by flow cytometry prior to cycle 1 and 2 of doxorubicin and cyclophosphamide and 1st and last administration of paclitaxel or paclitaxel/anti-HER2 therapy. Of 24 patients, 11, 6 and 7 patients were triple negative, HER2+ and hormone receptor+, respectively. Read More

    Immune biomarkers for chronic inflammation related complications in non-cancerous and cancerous diseases.
    Cancer Immunol Immunother 2017 Aug 3;66(8):1089-1101. Epub 2017 Jul 3.
    The Lautenberg Center for General and Tumor Immunology, Faculty of Medicine, Israel-Canada Medical Research Institute, The Hebrew University, POB 12272, 91120, Jerusalem, Israel.
    Chronic inflammation arising in a diverse range of non-cancerous and cancerous diseases, dysregulates immunity and exposes patients to a variety of complications. These include immunosuppression, tissue damage, cardiovascular diseases and more. In cancer, chronic inflammation and related immunosuppression can directly support tumor growth and dramatically reduce the efficacies of traditional treatments, as well as novel immune-based therapies, which require a functional immune system. Read More

    The clinical efficacy of first-generation carcinoembryonic antigen (CEACAM5)-specific CAR T cells is limited by poor persistence and transient pre-conditioning-dependent respiratory toxicity.
    Cancer Immunol Immunother 2017 Jun 28. Epub 2017 Jun 28.
    Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester Academic Health Science Centre, Wilmslow Road, Withington, Manchester, M20 4BX, UK.
    The primary aim of this clinical trial was to determine the feasibility of delivering first-generation CAR T cell therapy to patients with advanced, CEACAM5(+) malignancy. Secondary aims were to assess clinical efficacy, immune effector function and optimal dose of CAR T cells. Three cohorts of patients received increasing doses of CEACAM5(+)-specific CAR T cells after fludarabine pre-conditioning plus systemic IL2 support post T cell infusion. Read More

    LILRB receptor-mediated regulation of myeloid cell maturation and function.
    Cancer Immunol Immunother 2017 Aug 21;66(8):1079-1087. Epub 2017 Jun 21.
    Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, New York, NY, 10029, USA.
    The leukocyte immunoglobulin-like receptor (LILR) family comprises a set of paired immunomodulatory receptors expressed among human myeloid and lymphocyte cell populations. While six members of LILR subfamily A (LILRA) associate with membrane adaptors to signal via immunoreceptor tyrosine-based activating motifs (ITAM), LILR subfamily B (LILRB) members signal via multiple cytoplasmic immunoreceptor tyrosine-based inhibitory motifs (ITIM). Ligand specificity of some LILR family members has been studied in detail, but new perspective into the immunoregulatory aspects of this receptor family in human myeloid cells has been limited. Read More

    Critical biological parameters modulate affinity as a determinant of function in T-cell receptor gene-modified T-cells.
    Cancer Immunol Immunother 2017 Jun 20. Epub 2017 Jun 20.
    Department of Surgery, Cardinal Bernardin Cancer Center, Loyola University Chicago, 2160 S. 1st Ave, Bldg 112, Room 308, Maywood, IL, 60153, USA.
    T-cell receptor (TCR)-pMHC affinity has been generally accepted to be the most important factor dictating antigen recognition in gene-modified T-cells. As such, there is great interest in optimizing TCR-based immunotherapies by enhancing TCR affinity to augment the therapeutic benefit of TCR gene-modified T-cells in cancer patients. However, recent clinical trials using affinity-enhanced TCRs in adoptive cell transfer (ACT) have observed unintended and serious adverse events, including death, attributed to unpredicted off-tumor or off-target cross-reactivity. Read More

    Autoimmune diabetes induced by PD-1 inhibitor-retrospective analysis and pathogenesis: a case report and literature review.
    Cancer Immunol Immunother 2017 Jun 20. Epub 2017 Jun 20.
    AP-HP Diabetology Department, Lariboisière Hospital, Paris, France.
    Anti-PD-1 antibody treatment is approved in advanced melanoma and provides median overall survival over 24 months. The main treatment-related side effects are immune-related adverse events, which include rash, pruritus, vitiligo, thyroiditis, diarrhoea, hepatitis and pneumonitis. We report a case of autoimmune diabetes related to nivolumab treatment. Read More

    Blockade of CD112R and TIGIT signaling sensitizes human natural killer cell functions.
    Cancer Immunol Immunother 2017 Jun 16. Epub 2017 Jun 16.
    Department of Surgery, University of Colorado Anschutz Medical Campus, RC1-North Building, P18-8116, Aurora, CO, 80045, USA.
    Trastuzumab is the first-line drug to treat breast cancer with high Her2 expression. However, many cancers failed to respond, largely due to their resistance to NK cell-triggered antibody-dependent cellular cytotoxicity (ADCC). Poliovirus receptor (PVR)-like molecules are known to be important for lymphocyte functions. Read More

    A phase II study of ipilimumab plus temozolomide in patients with metastatic melanoma.
    Cancer Immunol Immunother 2017 Jun 13. Epub 2017 Jun 13.
    Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA.
    Checkpoint blockade has revolutionized the treatment of melanoma; however, it benefits only the minority of patients. Several agents have been combined with immunotherapy to improve T-cell activation and persistence including growth factor, chemotherapy, and radiation. Preclinical data suggest that temozolomide, which metabolizes to the same active compound as dacarbazine, selectively depletes regulatory T cells. Read More

    Phase I trial of antigen-targeted autologous dendritic cell-based vaccine with in vivo activation of inducible CD40 for advanced prostate cancer.
    Cancer Immunol Immunother 2017 Jun 12. Epub 2017 Jun 12.
    Bellicum Pharmaceuticals Inc., Houston, TX, USA.
    This phase I trial reports the safety and activity of BPX101, a second-generation antigen-targeted autologous antigen presenting cell (APC) vaccine in men with metastatic castration-resistant prostate cancer (mCRPC). To manufacture BPX101, APCs collected in a single leukapheresis were transduced with adenoviral vector Ad5f35 encoding inducible human (ih)-CD40, followed by incubation with protein PA001, which contains the extracellular domain of human prostate-specific membrane antigen. The ih-CD40 represents a modified chimeric version of the dendritic cell (DC) co-stimulatory molecule, CD40, which responds to a bioinert membrane-permeable activating dimerizer drug, rimiducid (AP1903), permitting temporally controlled, lymphoid-localized, DC-specific activation. Read More

    Enhanced stimulation of human tumor-specific T cells by dendritic cells matured in the presence of interferon-γ and multiple toll-like receptor agonists.
    Cancer Immunol Immunother 2017 Jun 10. Epub 2017 Jun 10.
    Department of Oncology-Pathology, Cancer Center Karolinska, Karolinska Institutet, Stockholm, Sweden.
    Dendritic cell (DC) vaccines have been demonstrated to elicit immunological responses in numerous cancer immunotherapy trials. However, long-lasting clinical effects are infrequent. We therefore sought to establish a protocol to generate DC with greater immunostimulatory capacity. Read More

    TGF-β1-silenced leukemia cell-derived exosomes target dendritic cells to induce potent anti-leukemic immunity in a mouse model.
    Cancer Immunol Immunother 2017 Jun 10. Epub 2017 Jun 10.
    Department of Hematology, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, 1665# Kongjiang Road, Shanghai, 200090, China.
    Tumor-derived exosomes (TEX) can induce a specific antitumor immune response and have been developed as a promising tumor vaccine. Despite promising preclinical data, TEX exhibit relatively low efficacy and limited clinical benefit in clinical trials. In the present study, we investigated whether exosomes from the TGF-β1 silenced L1210 cells (LEXTGF-β1si) can enhance the efficacy of DC-based vaccines. Read More

    Endoplasmic reticulum stress regulates tumor growth and anti-tumor immunity: a promising opportunity for cancer immunotherapy.
    Cancer Immunol Immunother 2017 Aug 2;66(8):1069-1078. Epub 2017 Jun 2.
    Department of Medicine, Georgia Cancer Center, Augusta University, 1410 Laney Walker Blvd, Room CN-4114, Augusta, GA, 30912, USA.
    The endoplasmic reticulum (ER) stress is a cellular process that occurs as a consequence of several stress circumstances, such as the accumulation of unfolded proteins in the lumen of the ER or distinct insults that disturb the ER normal function. Different conditions in the tumor microenvironment (TME), including hypoxia, nutrient deprivation, and the elevated production of reactive oxygen and nitrogen species destabilize the loading and dispatching of the newly synthesized proteins, triggering ER stress in cancer cells and tumor-infiltrating leukocytes. In order to cope with TME-induced ER stress, tumor and stromal cells initiate an adaptive response process that aims to resolve ER stress and to restore cellular homeostasis, which is referred as the unfolded protein responses (UPR). Read More

    In vitro differentiated plasmacytoid dendritic cells as a tool to induce anti-leukemia activity of natural killer cells.
    Cancer Immunol Immunother 2017 May 29. Epub 2017 May 29.
    Unité de recherche en hémato-oncologie Charles-Bruneau, Centre de Recherche du CHU Sainte-Justine, 3175, Côte Sainte-Catherine, Montreal, QC, H3T 1C5, Canada.
    Acute lymphoblastic leukemia (ALL) is believed to be resistant to NK cell-mediated killing. To overcome this resistance, we developed an innovative approach based on NK cell stimulation with Toll-like receptor (TLR)-activated plasmacytoid dendritic cells (pDC). The translation of this approach into the clinic requires the production of high numbers of human pDC. Read More

    Peripheral blood T cell alterations in newly diagnosed diffuse large B cell lymphoma patients and their long-term dynamics upon rituximab-based chemoimmunotherapy.
    Cancer Immunol Immunother 2017 May 29. Epub 2017 May 29.
    Department of Experimental Medicine, University La Sapienza, Viale Regina Elena 324, 00161, Rome, Italy.
    The importance of T cell-dependent immune responses in achieving long-term cure of chemoimmunotherapy-treated cancer patients is underscored by the recently described "vaccinal effect" exerted by therapeutic mAbs. In accordance, pre- and post-therapy peripheral blood lymphopenia represents a well-established negative prognostic factor in DLBCL. We analyzed the phenotypic and functional (IFNγ production, and Granzyme B (GrzB) cytotoxic granule marker expression) profile of peripheral blood T lymphocyte subsets ("conventional" CD4(+) and CD8(+), FOXP3(+)CD25(bright) Treg, and "innate-like" CD56(+)) in DLBCL patients at diagnosis, and assessed the long-term impact of R-CHOP chemoimmunotherapy, in a prospective study. Read More

    Macrophage-derived interleukin-1beta promotes human breast cancer cell migration and lymphatic adhesion in vitro.
    Cancer Immunol Immunother 2017 May 27. Epub 2017 May 27.
    Division of Cancer and Stem Cells, Translational and Radiation Biology Research Group, School of Medicine, Academic Clinical Oncology, University of Nottingham, Nottingham University Hospitals NHS Trust, City Hospital Campus, Nottingham, NG5 1PB, UK.
    Lymphovascular invasion (LVI), encompassing blood and lymphatic vessel invasion, is an important event in tumourigenesis. Macrophages within the tumour microenvironment are linked to the presence of LVI and angiogenesis. This study investigates the role of macrophage-derived, caspase-1-dependent interleukin-1beta (IL-1β) in an in vitro model of LVI. Read More

    CD45RA(-)Foxp3(high) regulatory T cells have a negative impact on the clinical outcome of head and neck squamous cell carcinoma.
    Cancer Immunol Immunother 2017 May 27. Epub 2017 May 27.
    Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.
    Background: Although regulatory T cells (Tregs) are thought to play an important role in immune suppression, their clinical significance in head and neck squamous cell carcinoma (HNSCC) is unclear. A recent study reported Tregs could be divided into functional subsets based on the expression of CD45RA and Foxp3.

    Method: The frequency of circulating Treg subsets was analyzed in patients with HNSCC and compared with the frequency in patients with benign tumors. Read More

    Decreased human leukocyte antigen A*02:01 frequency is associated with risk of glioma and existence of human cytomegalovirus: a case-control study in Northern China.
    Cancer Immunol Immunother 2017 May 18. Epub 2017 May 18.
    Department of Neurosurgery, The First Hospital of China Medical University, Nanjing Street 155, Heping District, Shenyang, 110001, China.
    Background: Human leukocyte antigens (HLAs) play an important role in host defense against viral infection and tumorigenesis. Human cytomegalovirus (HCMV) has been linked to glioma development. This study investigated the relationship between HLA distribution, presence of HCMV, and glioma development in a Han Chinese population. Read More

    Paracrine release of IL-2 and anti-CTLA-4 enhances the ability of artificial polymer antigen-presenting cells to expand antigen-specific T cells and inhibit tumor growth in a mouse model.
    Cancer Immunol Immunother 2017 May 13. Epub 2017 May 13.
    Department of Microbiology and Immunology, Medical School, Southeast University, 87 Dingjiaqiao Rd, Nanjing, 210009, Jiangsu, People's Republic of China.
    Accumulating evidence indicates that bead-based artificial antigen-presenting cells (aAPCs) are a powerful tool to induce antigen-specific T cell responses in vitro and in vivo. To date, most conventional aAPCs have been generated by coupling an antigen signal (signal 1) and one or two costimulatory signals, such as anti-CD28 with anti-LFA1 or anti-4-1BB (signal 2), onto the surfaces of cell-sized or nanoscale magnetic beads or polyester latex beads. The development of a biodegradable scaffold and the combined use of multiple costimulatory signals as well as third signals for putative clinical applications is the next step in the development of this technology. Read More

    Common extracellular matrix regulation of myeloid cell activity in the bone marrow and tumor microenvironments.
    Cancer Immunol Immunother 2017 Aug 13;66(8):1059-1067. Epub 2017 May 13.
    Molecular Immunology Unit, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Amadeo, 42, 20133, Milan, Italy.
    The complex interaction between cells undergoing transformation and the various stromal and immunological cell components of the tumor microenvironment (TME) crucially influences cancer progression and diversification, as well as endowing clinical and prognostic significance. The immunosuppression characterizing the TME depends on the recruitment and activation of different cell types including regulatory T cells, myeloid-derived suppressor cells, and tumor-associated macrophages. Less considered is the non-cellular component of the TME. Read More

    Dianthin-30 or gelonin versus monomethyl auristatin E, each configured with an anti-calcitonin receptor antibody, are differentially potent in vitro in high-grade glioma cell lines derived from glioblastoma.
    Cancer Immunol Immunother 2017 May 13. Epub 2017 May 13.
    Department of Medicine/Cardiology (Austin Health, Heidelberg), University of Melbourne, Lance Townsend Building, Level 10, Austin Campus, Studley Road, Heidelberg, VIC, 3084, Australia.
    We have reported that calcitonin receptor (CTR) is widely expressed in biopsies from the lethal brain tumour glioblastoma by malignant glioma and brain tumour-initiating cells (glioma stem cells) using anti-human CTR antibodies. A monoclonal antibody against an epitope within the extracellular domain of CTR was raised (mAb2C4) and chemically conjugated to either plant ribosome-inactivating proteins (RIPs) dianthin-30 or gelonin, or the drug monomethyl auristatin E (MMAE), and purified. In the high-grade glioma cell line (HGG, representing glioma stem cells) SB2b, in the presence of the triterpene glycoside SO1861, the EC50 for mAb2C4:dianthin was 10. Read More

    Zoledronic acid renders human M1 and M2 macrophages susceptible to Vδ2(+) γδ T cell cytotoxicity in a perforin-dependent manner.
    Cancer Immunol Immunother 2017 May 13. Epub 2017 May 13.
    Institute for Infection and Immunity, St. George's University of London, Cranmer Terrace, Tooting, London, SW17 0RE, UK.
    Vδ2(+) T cells are a subpopulation of γδ T cells in humans that are cytotoxic towards cells which accumulate isopentenyl pyrophosphate. The nitrogen-containing bisphosphonate, zoledronic acid (ZA), can induce tumour cell lines to accumulate isopentenyl pyrophosphate, thus rendering them more susceptible to Vδ2(+) T cell cytotoxicity. However, little is known about whether ZA renders other, non-malignant cell types susceptible. Read More

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