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Cancer Immunology, Immunotherapy: CII

Shu-Fen Chiang, Chih-Yang Huang, Tao-Wei Ke, Tsung-Wei Chen, Yu-Ching Lan, Ying-Shu You, William Tzu-Liang Chen, K S Clifford Chao
The expression of programmed cell death 1 ligand 1 (PD-L1) and interferon-γ (IFN-γ) is of great interest for the development of chemoradiotherapy and immune checkpoint inhibitor treatments. Patients with nodal metastasis (pN+) tend to have a poor prognosis, even after neoadjuvant chemoradiotherapy (neoCRT) and surgical treatment. In this study, we examined the roles of tumor PD-L1 and IFN-γ before and after neoCRT in locally advanced rectal cancer (LARC) patients. Our results demonstrate that patients with high PD-L1 expression in post-neoCRT tissues exhibit improved 5-year disease-free survival (DFS) and overall survival (OS) compared with those with low PD-L1 expression (p < 0...
November 17, 2018: Cancer Immunology, Immunotherapy: CII
Akihiro Tsuboi, Naoya Hashimoto, Fumihiro Fujiki, Soyoko Morimoto, Naoki Kagawa, Hiroko Nakajima, Naoki Hosen, Sumiyuki Nishida, Jun Nakata, Satoshi Morita, Junichi Sakamoto, Yusuke Oji, Yoshihiro Oka, Haruo Sugiyama
PURPOSE: The safety and clinical efficacy of WT1 human leukocyte antigen (HLA) class I peptide vaccine have been established, but the safety of a cocktail vaccine of WT1 HLA class I and II peptides has not. To verify its safety, we performed a phase I clinical trial for patients with recurrent malignant gliomas and assessed the immunological responses and survival data. PATIENTS AND METHODS: Fourteen HLA-A*24:02-positive patients with recurrent malignant glioma (2 with grade 3, 12 with grade 4) were enrolled...
November 14, 2018: Cancer Immunology, Immunotherapy: CII
Wagner A Poles, Erika E Nishi, Mariana B de Oliveira, Angela I P Eugênio, Tathiana A de Andrade, Antonio Hugo F M Campos, Ruy R de Campos, José Vassallo, Antonio C Alves, Cristovam Scapulatempo Neto, Roberto Antonio Pinto Paes, Gilles Landman, Maria Cláudia N Zerbini, Gisele W B Colleoni
Aging immune deterioration and Epstein-Barr (EBV) intrinsic mechanisms play an essential role in EBV-positive diffuse large B-cell lymphoma (DLBCL) of the elderly (EBV + DLBCLe) pathogenesis, through the expression of viral proteins, interaction with host molecules and epigenetic regulation, such as miR-155, required for induction of M1 phenotype of macrophages. This study aims to evaluate the relationship between macrophage polarization pattern in the tumor microenvironment and relative expression of miR-155 in EBV + DLBCLe and EBV-negative DLBCL patients...
November 14, 2018: Cancer Immunology, Immunotherapy: CII
Charlotte M Huijts, Inge M Werter, Sinéad M Lougheed, Ruben S Goedegebuure, Carla M van Herpen, Paul Hamberg, Metin Tascilar, John B Haanen, Henk M Verheul, Tanja D de Gruijl, Hans J van der Vliet
mTOR inhibitors are frequently used in the treatment of metastatic renal cell cancer (mRCC). mTOR regulates cell growth, proliferation, angiogenesis, and survival, and additionally plays an important role in immune regulation. Since mTOR inhibitors were shown to benefit immunosuppressive regulatory T-cell (Treg) expansion, this might suppress antitumor immune responses. Metronomic cyclophosphamide (CTX) was shown to selectively deplete Tregs. This study was, therefore, designed to determine the optimal dosage and schedule of CTX when combined with everolimus to prevent this potentially detrimental Treg expansion...
November 9, 2018: Cancer Immunology, Immunotherapy: CII
Matthieu Besneux, Alexander Greenshields-Watson, Martin J Scurr, Bruce J MacLachlan, Adam Christian, Michael M Davies, Rachel Hargest, Simon Phillips, Andrew Godkin, Awen Gallimore
The oncofoetal antigen 5T4 is a promising T cell target in the context of colorectal cancer, as demonstrated by a recent clinical study where 5T4-specific T cell responses, induced by vaccination or cyclophosphamide, were associated with a significantly prolonged survival of patients with metastatic disease. Whilst Th1-type (IFN-γ+ ) responses specific to 5T4, and other oncofoetal antigens, are often readily detectable in early stage CRC patients and healthy donors, their activity is suppressed as the cancer progresses by CD4+ CD25hi Foxp3+ regulatory T cells (Treg) which contribute to the immunosuppressive environment conducive to tumour growth...
November 7, 2018: Cancer Immunology, Immunotherapy: CII
Jingjing Zhu, Pierre-Florent Petit, Benoit J Van den Eynde
Immunotherapy based on checkpoint inhibitors is providing substantial clinical benefit, but only to a minority of cancer patients. The current priority is to understand why the majority of patients fail to respond. Besides T-cell dysfunction, T-cell apoptosis was reported in several recent studies as a relevant mechanism of tumoral immune resistance. Several death receptors (Fas, DR3, DR4, DR5, TNFR1) can trigger apoptosis when activated by their respective ligands. In this review, we discuss the immunomodulatory role of the main death receptors and how these are shaping the tumor microenvironment, with a focus on Fas and its ligand...
November 7, 2018: Cancer Immunology, Immunotherapy: CII
Wenli Yuan, Deyao Deng, Hongchao Jiang, Changling Tu, Xueqin Shang, Hongchun He, Ruize Niu, Jian Dong
Colorectal cancer (CRC) with high-level microsatellite instability (MSI-H) tends to be associated with a better response to programmed death receptor-1 (PD-1) blockade than does microsatellite stable CRC. However, emerging evidence makes the use of programmed death ligand-1 (PD-L1) as a biomarker problematic. Here, we sought to characterize the interactions between PD-L1 expression and the response to PD-1 blockade therapy in BALB/c mice with a subcutaneous tumor challenge. We further focused on interferon gamma (IFNγ)-induced PD-L1 expression in an in vitro setting to evaluate the responsiveness to IFNγ exposure and the specific signaling of PD-1 in HCT116 and SW480 cell lines...
November 7, 2018: Cancer Immunology, Immunotherapy: CII
Dmitri Loukinov
Cancer vaccines have great potential in the fight against metastatic malignancies. Current anti-tumor immunotherapy is hindered by existing tolerance to tumor-associated antigens (TAA) and tumor escape using various mechanisms, highlighting the need for improved targets for immunotherapy. The cancer-testis antigen CTCFL/BORIS was discovered 16 years ago and possesses all features necessary for an ideal TAA. Recently CTCFL/BORIS has received additional attention as a target expressed in cancer stem cells (CSC)...
November 2, 2018: Cancer Immunology, Immunotherapy: CII
Laura A Vitale, Lawrence J Thomas, Li-Zhen He, Thomas O'Neill, Jenifer Widger, Andrea Crocker, Karuna Sundarapandiyan, James R Storey, Eric M Forsberg, Jeffrey Weidlick, April R Baronas, Lauren E Gergel, James M Boyer, Crystal Sisson, Joel Goldstein, Henry C Marsh, Tibor Keler
Limitations of immunotherapy include poorly functioning events early in the immune response cycle, such as efficient antigen presentation and T cell priming. CD40 signaling in dendritic cells leads to upregulation of cell surface costimulatory and MHC molecules and the generation of cytokines, which promotes effective priming of CD8+ effector T cells while minimizing T cell anergy and the generation of regulatory T cells. This naturally occurs through interaction with CD40 ligand (CD40L) expressed on CD4+ T-helper cells...
October 31, 2018: Cancer Immunology, Immunotherapy: CII
Jacqueline E Mann, Joshua D Smith, Andrew C Birkeland, Emily Bellile, Paul Swiecicki, Michelle Mierzwa, Steven B Chinn, Andrew G Shuman, Kelly M Malloy, Keith A Casper, Scott A McLean, Jeffery S Moyer, Gregory T Wolf, Carol R Bradford, Mark E Prince, Thomas E Carey, Jonathan B McHugh, Matthew E Spector, J Chad Brenner
BACKGROUND: Recurrent laryngeal squamous cell carcinomas (LSCCs) are associated with poor outcomes, without reliable biomarkers to identify patients who may benefit from adjuvant therapies. Given the emergence of tumor-infiltrating lymphocytes (TIL) as a biomarker in head and neck squamous cell carcinoma, we generated predictive models to understand the utility of CD4+ , CD8+ and/or CD103+ TIL status in patients with advanced LSCC. METHODS: Tissue microarrays were constructed from salvage laryngectomy specimens of 183 patients with recurrent/persistent LSCC and independently stained for CD4+ , CD8+ , and CD103+ TIL content...
October 25, 2018: Cancer Immunology, Immunotherapy: CII
Yi-Hui Wen, Han-Qing Lin, Hang Li, Yi Zhao, Vivian Wai Yan Lui, Lin Chen, Xing-Mei Wu, Wei Sun, Wei-Ping Wen
Regulatory T cells (Tregs) mediate immunosuppressive signals that can contribute to the progression of head and neck squamous cell carcinoma (HNSCC). Interleukin-33 (IL-33) is defined as an 'alarmin', an endogenous factor that is expressed during tissue and cell damage, which has been shown to promote Treg proliferation in non-lymphoid organs. However, the interaction between IL-33 and Tregs in the HNSCC tumor microenvironment remains uncertain. In this study, we examined IL-33+ and Foxp3+ cells by immunohistochemistry in 68 laryngeal squamous cell cancer patients, followed by functional analysis of IL-33 in Tregs...
October 25, 2018: Cancer Immunology, Immunotherapy: CII
Daisuke Umezu, Nana Okada, Yukimi Sakoda, Keishi Adachi, Toshiyasu Ojima, Hiroki Yamaue, Masatoshi Eto, Koji Tamada
Although a role of PD-L1 in the suppression of anti-tumor immunity and its value as a predictive biomarker has been suggested by various preclinical and clinical studies, the precise mechanisms how PD-L1 and PD-L2, another ligand of PD-1, regulate anti-tumor immunity in the tumor microenvironment are yet to be fully explored. Here, we address this issue using PD-L1-deficient tumor cells, PD-L1-knockout (KO) mice, anti-PD-L1 monoclonal antibody (mAb), and anti-PD-L2 mAb. Firstly, PD-L1-deficient or competent tumor cells were inoculated into wild-type or PD-L1-KO mice...
October 24, 2018: Cancer Immunology, Immunotherapy: CII
Giada Amodio, Joanna Cichy, Patricia Conde, Gianluca Matteoli, Aurélie Moreau, Jordi Ochando, Barbaros H Oral, Michaela Pekarova, Elizabeth J Ryan, Johannes Roth, Yahya Sohrabi, Maria-Cristina Cuturi, Silvia Gregori
Myeloid cells play a pivotal role in regulating innate and adaptive immune responses. In inflammation, autoimmunity, and after transplantation, myeloid cells have contrasting roles: on the one hand they initiate the immune response, promoting activation and expansion of effector T-cells, and on the other, they counter-regulate inflammation, maintain tissue homeostasis, and promote tolerance. The latter activities are mediated by several myeloid cells including polymorphonuclear neutrophils, macrophages, myeloid-derived suppressor cells, and dendritic cells...
October 24, 2018: Cancer Immunology, Immunotherapy: CII
Boke Zhang, Yan Du, Yiqing He, Yiwen Liu, Guoliang Zhang, Cuixia Yang, Feng Gao
As a major component of the microenvironment of solid tumors, tumor-associated macrophages (TAMs) facilitate tumor progression. Intermediate-sized hyaluronan (INT-HA) fragments have an immunological function in cell differentiation; however, their role in promoting the polarization of non-activated macrophages to an M2-like TAM phenotype has not been characterized, and the underlying mechanisms remain unclear. Here, we used a miRNA microarray to find that some miRNAs (especially miR-935) were differentially regulated in INT-HA-induced M2-like macrophages...
October 19, 2018: Cancer Immunology, Immunotherapy: CII
Tyler R McCaw, Mei Li, Dmytro Starenki, Sara J Cooper, Mingyong Liu, Selene Meza-Perez, Rebecca C Arend, Donald J Buchsbaum, Andres Forero, Troy D Randall
The expression of MHC class II molecules (MHCII) on tumor cells correlates with survival and responsiveness to immunotherapy. However, the mechanisms underlying these observations are poorly defined. Using a murine breast tumor line, we showed that MHCII-expressing tumors grew more slowly than controls and recruited more functional CD4+ and CD8+ T cells. In addition, MHCII-expressing tumors contained more TCR clonotypes expanded to a larger degree than control tumors. Functional CD8+ T cells in tumors depended on CD4+ T cells...
October 17, 2018: Cancer Immunology, Immunotherapy: CII
Hanna Grauers Wiktorin, Malin S Nilsson, Roberta Kiffin, Frida Ewald Sander, Brianna Lenox, Anna Rydström, Kristoffer Hellstrand, Anna Martner
Myeloid-derived suppressor cells (MDSCs) are immature monocytes and granulocytes that impede immune-mediated clearance of malignant cells by multiple mechanisms, including the formation of immunosuppressive reactive oxygen species (ROS) via the myeloid cell NADPH oxidase (NOX2). Histamine dihydrochloride (HDC), a NOX2 inhibitor, exerts anti-cancer efficacy in experimental tumor models but the detailed mechanisms are insufficiently understood. To determine effects of HDC on the MDSC compartment we utilized three murine cancer models known to entail accumulation of MDSC, i...
October 12, 2018: Cancer Immunology, Immunotherapy: CII
Aliyah M Weinstein, Nicolas A Giraldo, Florent Petitprez, Catherine Julie, Laetitia Lacroix, Frédérique Peschaud, Jean-François Emile, Laetitia Marisa, Wolf H Fridman, Walter J Storkus, Catherine Sautès-Fridman
IL-1 family cytokines play a dual role in the gut, with different family members contributing either protective or pathogenic effects. IL-36γ is an IL-1 family cytokine involved in polarizing type-1 immune responses. However, its function in the gut, including in colorectal cancer pathogenesis, is not well appreciated. In a murine model of colon carcinoma, IL-36γ controls tertiary lymphoid structure formation and promotes a type-1 immune response concurrently with a decrease in expression of immune checkpoint molecules in the tumor microenvironment...
October 12, 2018: Cancer Immunology, Immunotherapy: CII
Maria Pia Pistillo, Vincenzo Fontana, Anna Morabito, Beatrice Dozin, Stefania Laurent, Roberta Carosio, Barbara Banelli, Francesca Ferrero, Laura Spano, Enrica Tanda, Pier Francesco Ferrucci, Chiara Martinoli, Emilia Cocorocchio, Michele Guida, Stefania Tommasi, Federica De Galitiis, Elena Pagani, Gian Carlo Antonini Cappellini, Paolo Marchetti, Pietro Quaglino, Paolo Fava, Simona Osella-Abate, Paolo Antonio Ascierto, Mariaelena Capone, Ester Simeone, Massimo Romani, Francesco Spagnolo, Paola Queirolo
CTLA-4 blockade by means of ipilimumab (IPI) potentiates the immune response and improves overall survival (OS) in a minority of metastatic melanoma (MM) patients. We investigated the role of soluble CTLA-4 (sCTLA-4) as a possible biomarker for identifying this subset of patients. sCTLA-4 levels were analyzed at baseline in sera from 113 IPI-treated MM patients by ELISA, and the median value (200 pg/ml) was used to create two equally sized subgroups. Associations of sCTLA-4 with best overall response (BOR) to IPI and immune-related adverse events (irAEs) were evaluated through logistic regression...
October 11, 2018: Cancer Immunology, Immunotherapy: CII
Wei Wang, Wai-Ching Lam, Ling Chen
Blockade of programmed cell death-1 (PD-1) has become one of the most promising immunotherapies for many human cancers. However, immune-related adverse events can be produced by anti-PD-1 therapy. Uveitis is a rare but potentially devastating side effect of anti-PD-1 therapy. Delay in diagnosis or improper treatment may eventually lead to irreversible blindness. Therefore, it is important for the oncologist and the ophthalmologist to recognize and manage this adverse event properly in patients receiving anti-PD-1 therapy in a timely manner...
October 11, 2018: Cancer Immunology, Immunotherapy: CII
Wen Zhang, Xu Lu, Peilin Cui, Chunmei Piao, Man Xiao, Xuesong Liu, Yue Wang, Xuan Wu, Jingwei Liu, Lin Yang
Dendritic cell (DC)-based immunotherapies have been created for a broad expanse of cancers, and DC vaccines prepared with Wilms' tumor protein 1 (WT1) peptides have shown great therapeutic efficacy in these diseases. In this paper, we report the results of a phase I/II study of a DC-based vaccination for advanced breast, ovarian, and gastric cancers, and we offer evidence that patients can be effectively vaccinated with autologous DCs pulsed with WT1 peptide. There were ten patients who took part in this clinical study; they were treated biweekly with a WT1 peptide-pulsed DC vaccination, with toxicity and clinical and immunological responses as the principal endpoints...
October 10, 2018: Cancer Immunology, Immunotherapy: CII
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