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Bo Yang, Tingjun Liu, Yang Qu, Hangbo Liu, Song Guo Zheng, Bin Cheng, Jianbo Sun
Head and neck cancer is the 6th most common malignancy worldwide and urgently requires novel therapy methods to change the situation of low 5-years survival rate and poor prognosis. Targeted therapy provides more precision, higher efficiency while lower adverse effects than traditional treatments like surgery, radiotherapy, and chemotherapy. Blockade of PD-1 pathway with antibodies against PD-1 or PD-L1 is such a typical targeted therapy which reconstitutes anti-tumor activity of T cell in treatments of cancers, especially those highly expressing PD-L1, including head and neck cancers...
2018: Frontiers in Oncology
Junseong Park, Chang Gon Kim, Jin-Kyoung Shim, Jong Hoon Kim, Hoyoung Lee, Jae Eun Lee, Min Hwan Kim, Keeok Haam, Inkyung Jung, Su-Hyung Park, Jong Hee Chang, Eui-Cheol Shin, Seok-Gu Kang
Background : Although programmed death-1 (PD-1) blockade is effective in treating several types of cancer, the efficacy of this agent in glioblastoma (GBM) is largely unknown. Methods : We evaluated therapeutic effects of anti-PD-1, temozolomide (TMZ), and their combination in an orthotopic murine GBM model. The phenotype, number, and composition of lymphocytes were evaluated using flow cytometry. Transcriptional profiles of tumor tissues were analyzed using microarrays. Generation of antitumor immunological memory was investigated upon rechallenge...
2019: Oncoimmunology
Sebastian Kruse, Marleen Büchler, Philipp Uhl, Max Sauter, Philipp Scherer, Tammy C T Lan, Samantha Zottnick, Alexandra Klevenz, Ruwen Yang, Frank Rösl, Walter Mier, Angelika B Riemer
Therapeutic vaccination as a treatment option for HPV-induced cancers is actively pursued because the two HPV proteins E6 and E7 represent ideal targets for immunotherapy, as they are non-self and expressed in all tumor stages. MHC-humanized mice are valuable tools for the study of therapeutic cancer vaccines - given the availability of a suitable tumor model. Here, we present for the first time an HPV16 tumor model suitable for fully MHC-humanized A2.DR1 mice, PAP-A2 cells, which in contrast to existing HPV16 tumor models allows the exclusive study of HLA-A2- and DR1-mediated immune responses, without any interfering murine MHC-presented epitopes...
2019: Oncoimmunology
Julia Krombach, Roman Hennel, Nikko Brix, Michael Orth, Ulrike Schoetz, Anne Ernst, Jessica Schuster, Gabriele Zuchtriegel, Christoph A Reichel, Susanne Bierschenk, Markus Sperandio, Thomas Vogl, Steffen Unkel, Claus Belka, Kirsten Lauber
The major goal of radiotherapy is the induction of tumor cell death. Additionally, radiotherapy can function as in situ cancer vaccination by exposing tumor antigens and providing adjuvants for anti-tumor immune priming. In this regard, the mode of tumor cell death and the repertoire of released damage-associated molecular patterns (DAMPs) are crucial. However, optimal dosing and fractionation of radiotherapy remain controversial. Here, we examined the initial steps of anti-tumor immune priming by different radiation regimens (20 Gy, 4 × 2 Gy, 2 Gy, 0 Gy) with cell lines of triple-negative breast cancer in vitro and in vivo ...
2019: Oncoimmunology
Joanna Walkowska, Thomas Kallemose, Göran Jönsson, Mats Jönsson, Ove Andersen, Mads Hald Andersen, Inge Marie Svane, Anne Langkilde, Mef Nilbert, Christina Therkildsen
Colorectal cancers associated with Lynch syndrome are characterized by defective mismatch repair, microsatellite instability, high mutation rates, and a highly immunogenic environment. These features define a subset of cancer with a favorable prognosis and high likelihood to respond to treatment with anti-programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) drugs. With the aim to define immune-evasive mechanisms and a potential impact hereof in colorectal cancers from Lynch syndrome versus hereditary cases with retained mismatch repair function, we immunohistochemically and transcriptionally profiled 270 tumors...
2019: Oncoimmunology
Jiajun Wang, Li Liu, Qi Bai, Chenzhang Ou, Ying Xiong, Yang Qu, Zewei Wang, Yu Xia, Jianming Guo, Jiejie Xu
Tumor-infiltrating neutrophils (TINs) show diverse predictive effects in the context of different cancer types and therapeutic regimens. In this study we investigated their relevance with therapeutic effect of tyrosine kinase inhibitors (TKIs) in metastatic renal cell carcinoma (mRCC). Two independent datasets including 271 mRCC patients treated by TKIs or IL-2/IFN-α based immunotherapy were retrospective included, and TINs were detected by immunohistochemistry. The presence of TINs was observed in 50 (45...
2019: Oncoimmunology
Alfredo Perales-Puchalt, Nikolaos Svoronos, Daniel O Villarreal, Urvi Zankharia, Emma Reuschel, Krzysztof Wojtak, Kyle K Payne, Elizabeth K Duperret, Kar Muthumani, Jose R Conejo-Garcia, David B Weiner
Ovarian cancer is frequently diagnosed as peritoneal carcinomatosis. Unlike other tumor locations, the peritoneal cavity is commonly exposed to gut-breaching and ascending genital microorganisms and has a unique immune environment. IL-33 is a local cytokine that can activate innate and adaptive immunity. We studied the effectiveness of local IL-33 delivery in the treatment of cancer that has metastasized to the peritoneal cavity. Direct peritoneal administration of IL-33 delayed the progression of metastatic peritoneal cancer...
2019: Oncoimmunology
Seong-Ho Kang, Bhumsuk Keam, Yong-Oon Ahn, Ha-Ram Park, Miso Kim, Tae Min Kim, Dong-Wan Kim, Dae Seog Heo
Major histocompatibility complex (MHC) class I downregulation is the primary immune evasion mechanism associated with failure in anti-PD-1/PD-L1 blockade therapies for cancer. Here, we examined the role of MEK signaling pathway inhibition in head and neck squamous cell carcinoma (HNSCC) both in vitro and in vivo . We found that trametinib, a small molecule inhibitor of MEK, significantly enhanced MHC class I and PD-L1 expression in human HNSCC cell lines, and this occurred via STAT3 activation. Trametinib also further upregulated the increase in CXCL9 and CXCL10 expression caused by IFN-γ in HNSCC cells, which is associated with T cell infiltration in tumor tissues...
2019: Oncoimmunology
Hans A Schlößer, Martin Thelen, Axel Lechner, Kerstin Wennhold, Maria A Garcia-Marquez, Sacha I Rothschild, Elena Staib, Thomas Zander, Dirk Beutner, Birgit Gathof, Ramona Gilles, Engin Cukuroglu, Jonathan Göke, Alexander Shimabukuro-Vornhagen, Uta Drebber, Alexander Quaas, Christiane J Bruns, Arnulf H Hölscher, Michael S Von Bergwelt-Baildon
Tumor-infiltrating lymphocytes (TILs) are correlated to prognosis of several kinds of cancer. Most studies focused on T cells, while the role of tumor-associated B cells (TABs) has only recently gained more attention. TABs contain subpopulations with distinct functions, potentially promoting or inhibiting immune responses. This study provides a detailed analysis of TABs in gastro-esophageal adenocarcinoma (EAC). Flow cytometric analyses of single cell suspensions of tumor samples, mucosa, lymph nodes and peripheral blood mononuclear cells (PBMC) of EAC patients and healthy controls revealed a distinct B cell compartment in cancer patients...
2019: Oncoimmunology
Peng Yue, Taylor Harper, Silvia M Bacot, Monica Chowdhury, Shiowjen Lee, Adovi Akue, Mark A Kukuruga, Tao Wang, Gerald M Feldman
Immune checkpoint inhibitors (ICIs) such as the anti-PD-1 antibody Nivolumab, achieve remarkable clinical efficacy in patients with late stage cancers. However, only a small subset of patients benefit from this therapy. Numerous clinical trials are underway testing whether combining ICIs with other anti-cancer therapies can increase this response rate. For example, anti-PD-1/PD-L1 therapy combined with MAP kinase inhibition using BRAF inhibitors (BRAFi) and/or MEK inhibitors (MEKi) are in development for treatment of late stage melanomas...
2019: Oncoimmunology
Jonathan G Pol, Sergio A Acuna, Beta Yadollahi, Nan Tang, Kyle B Stephenson, Matthew J Atherton, David Hanwell, Alexander El-Warrak, Alyssa Goldstein, Badru Moloo, Patricia V Turner, Roberto Lopez, Sandra LaFrance, Carole Evelegh, Galina Denisova, Robin Parsons, Jamie Millar, Gautier Stoll, Chantal G Martin, Julia Pomoransky, Caroline J Breitbach, Jonathan L Bramson, John C Bell, Yonghong Wan, David F Stojdl, Brian D Lichty, J Andrea McCart
Multiple immunotherapeutics have been approved for cancer patients, however advanced solid tumors are frequently refractory to treatment. We evaluated the safety and immunogenicity of a vaccination approach with multimodal oncolytic potential in non-human primates (NHP) ( Macaca fascicularis ). Primates received a replication-deficient adenoviral prime, boosted by the oncolytic Maraba MG1 rhabdovirus. Both vectors expressed the human MAGE-A3. No severe adverse events were observed. Boosting with MG1-MAGEA3 induced an expansion of hMAGE-A3-specific CD4+ and CD8+ T-cells with the latter peaking at remarkable levels and persisting for several months...
2019: Oncoimmunology
Ruocong Zhao, Lin Cheng, Zhiwu Jiang, Xinru Wei, Baiheng Li, Qiting Wu, Suna Wang, Simiao Lin, Youguo Long, Xuchao Zhang, Yilong Wu, Xin Du, Duanqing Pei, Pentao Liu, Yangqiu Li, Shuzhong Cui, Yao Yao, Peng Li
Chimeric antigen receptor (CAR) T cell immunotherapies have shown remarkable efficacy in treating multiple types of hematological malignancies but are not sufficiently effective at treating solid tumors. NKG2D is a strong activating receptor for NK cells and a co-stimulatory receptor for T cells. NKG2D signal transduction depends on DNAX-activating protein 10 (DAP10). Here, we introduced the cytoplasmic domain of DAP10 into the second-generation CARs M28z and G28z to generate M28z10 and G28z10, which target mesothelin (MSLN) and glypican 3 (GPC3), respectively...
2019: Oncoimmunology
Katsunobu Hagihara, Stephen Chan, Li Zhang, David Y Oh, Xiao X Wei, Jeffry Simko, Lawrence Fong
Sipuleucel-T is the only FDA-approved immunotherapy for metastatic castration-resistant prostate cancer. The mechanism by which this treatment improves survival is not fully understood. We have previously shown that this treatment can induce the recruitment of CD4 and CD8 T cells to the tumor microenvironment. In this study, we examined the functional state of these T cells through gene expression profiling. We found that the magnitude of T cell signatures correlated with the frequency of T cells as measured by immunohistochemistry...
2019: Oncoimmunology
Patrizia Leone, Giuseppe Di Lernia, Antonio Giovanni Solimando, Sebastiano Cicco, Ilaria Saltarella, Aurelia Lamanuzzi, Roberto Ria, Maria Antonia Frassanito, Maurilio Ponzoni, Paolo Ditonno, Franco Dammacco, Vito Racanelli, Angelo Vacca
Endothelial cells (EC) line the bone marrow microvasculature and are in close contact with CD8+ T cells that come and go across the permeable capillaries. Because of these intimate interactions, we investigated the capacity of EC to act as antigen-presenting cells (APC) and modulate CD8+ T cell activation and proliferation in bone marrow of patients with multiple myeloma (MM) and monoclonal gammopathy of undetermined significance. We found that EC from MM patients show a phenotype of semi-professional APC given that they express low levels of the co-stimulatory molecules CD40, CD80 and CD86, and of the inducible co-stimulator ligand (ICOSL)...
2019: Oncoimmunology
Qinchuan Wang, Justin R Gregg, Jian Gu, Yuanqing Ye, David W Chang, John W Davis, Timothy C Thompson, Jeri Kim, Christopher J Logothetis, Xifeng Wu
Determining prostate cancer (PCa) aggressiveness and reclassification are critical events during the treatment of localized disease and for patients undergoing active surveillance (AS). Since T cells play major roles in cancer surveillance and elimination, we aimed to identify genetic biomarkers related to T cell cancer immune response which are predictive of aggressiveness and reclassification risks in localized PCa. The genotypes of 3,586 single nucleotide polymorphisms (SNPs) from T cell cancer immune response pathways were analyzed in 1762 patients with localized disease and 393 who elected AS...
2019: Oncoimmunology
Emilie T E Gross, Carlos D Peinado, Yujin Jung, Semi Han, Beichen Liu, Endi K Santosa, Jack D Bui
The cancer stem cell (CSC) paradigm posits that specific cells within a tumor, so-called CSC-like cells, have differing levels of tumorigenicity and chemoresistance. Original studies of CSCs identified them in human cancers and utilized mouse xenograft models to define the cancer initiating properties of these cells, thereby hampering the understanding of how immunity could affect CSCs. Indeed, few studies have characterized CSCs in the context of cancer immunoediting, and it is currently not clear how immunity could impact on the levels or stem-like behavior of CSCs...
2019: Oncoimmunology
Magdalena Niedzielska, Elisabeth Israelsson, Bastian Angermann, Benjamin S Sidders, Maryam Clausen, Matthew Catley, Rajneesh Malhotra, Céline Dumont
As we learn more about how immune responses occur in situ , it is becoming clear that each organ/tissue is characterized with its own anatomy and microenvironment which may affect and even determine the outcome of the immune responses. With emerging data from animal studies showing that regulatory T cells infiltrating non-lymphoid tissues exhibit unique phenotypes and transcriptional signatures and display functions beyond their well-established suppressive roles, there is an urgent need to explore the function of tissue Treg cells in humans...
November 16, 2018: Oncotarget
Nobuyuki Bandoh, Toshiaki Akahane, Takashi Goto, Michihisa Kono, Haruyuki Ichikawa, Takahiro Sawada, Tomomi Yamaguchi, Hiroshi Nakano, Yumiko Kawase, Yasutaka Kato, Hajime Kamada, Yasuaki Harabuchi, Kazuo Shimizu, Hiroshi Nishihara
Thyroid carcinoma (TC) has characteristic genetic alterations, including point mutations in proto-oncogenes and chromosomal rearrangements that vary by histologic subtype. Recent developments in next-generation sequencing (NGS) technology enable simultaneous analysis of cancer-associated genes of interest, thus improving diagnostic accuracy and allowing precise personalized treatment for human cancer. A total of 50 patients who underwent thyroidectomy between 2014 and 2016 at Hokuto Hospital were enrolled. Total DNA was extracted from formalin-fixed, paraffin-embedded tissue sections and quantified...
December 2018: Oncology Letters
Sandra Meršaková, Veronika Holubeková, Marián Grendár, Jozef Višňovský, Marcela Ňachajová, Michal Kalman, Erik Kúdela, Pavol Žúbor, Tibor Bielik, Zora Lasabová, Ján Danko
Cervical cancer (CC) is the second most common type of cancer affecting the female population. The development of CC takes several years, and involves a precancerous stage known as cervical intraepithelial neoplasia (CIN). A key factor in the development of disease is the human papillomavirus (HPV) infection, which initiates carcinogenesis. Furthermore, CC is also impacted by epigenetic changes such as DNA methylation, which causes activation or exclusion of certain genes, and the hypermethylation of cytosines in promoters, thereby switching off previously active genes...
December 2018: Oncology Letters
Yan Xia, Xiaopeng Tian, Juntao Wang, Dongjuan Qiao, Xianhao Liu, Liang Xiao, Wenli Liang, Dongcheng Ban, Junjun Chu, Jiaming Yu, Rongfu Wang, Geng Tian, Mingjun Wang
This article presented a case of a human leukocyte antigen (HLA)-A2-positive patient with advanced cancer/testis antigen New York esophageal squamous cell carcinoma-1 (NY-ESO-1) expressing lung adenocarcinoma (LADC) who received adoptive cell therapy of T cell receptor engineered-T cells (TCR-T cells) targeting the cancer-testis antigen NY-ESO-1. The appropriate clinical and laboratory assessments were conducted to investigate the safety and efficacy of this therapy for this lung cancer patient. The patient had a clinical response to and was well-tolerated with this therapy in the clinical trial...
December 2018: Oncology Letters
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