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Anti-tumor T cell response

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https://www.readbyqxmd.com/read/28734176/cancer-immunotherapy-moving-forward-with-peptide-t-cell-vaccines
#1
REVIEW
Takumi Kumai, Aaron Fan, Yasuaki Harabuchi, Esteban Celis
Recent advances in cancer immunology, such as the discovery of immune checkpoint inhibitors, have validated immune cells as potential key players for effective cancer treatment. The efficacy of these therapies seems to be codependent on a tumor-reactive T lymphocyte response. For many years, numerous attempts and strategies in developing vaccines to generate tumor-reactive T cells have yielded poor results in the clinic due to suboptimal immunogenicity and the inability to overcome an immunosuppressive tumor microenvironment...
July 19, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28733709/il-4-blockade-alters-the-tumor-microenvironment-and-augments-the-response-to-cancer-immunotherapy-in-a-mouse-model
#2
Shuku-Ei Ito, Hidekazu Shirota, Yuki Kasahara, Ken Saijo, Chikashi Ishioka
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. Current results demonstrate that the administration of a neutralizing antibody against IL-4 enhances anti-tumor immunity and delays tumor progression. IL-4 blockade also alters inflammation in the tumor microenvironment, reducing the generation of both immunosuppressive M2 macrophages and myeloid-derived suppressor cells, and enhancing tumor-specific cytotoxic T lymphocytes...
July 21, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28733529/immunotherapy-of-wap-tnp-mice-with-early-stage-mammary-gland-tumors
#3
Michael Bruns, Wolfgang Deppert
The SV40 transgenic BALB/c mouse based WAP-T/WAP-TNP model for triple-negative breast cancer allows the analysis of parameters influencing immunotherapeutic approaches. Except for WAP-TNP tumors expressing the immune-dominant LCMV NP-epitope within SV40 T-antigen (T-AgNP) which is not expressed by T-Ag of WAP-T tumors, the tumors are extremely similar. Comparative anti-PD1/PD-L1 immunotherapy of WAP-T and WAP-TNP mice supported the hypothesis that the immunogenicity of tumor antigen T-cell epitopes strongly influences the success of immune checkpoint blockade therapy, with highly immunogenic T-cell epitopes favoring rapid CTL exhaustion...
June 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28732279/turbocharging-vaccines-emerging-adjuvants-for-dendritic-cell-based-therapeutic-cancer-vaccines
#4
REVIEW
Mansi Saxena, Nina Bhardwaj
Development of therapeutic cancer vaccines has been hindered by the many pro-tumorigenic mechanisms at play in cancer patients that serve to suppress both antigen presenting cells and T cells. In face of these obstacles, cancer vaccines are most likely to promote anti-tumorigenic immune responses only when formulated with strong adjuvants, and in combination with new immune interventions designed to reverse immune suppression and exhaustion of T cells in the tumor microenvironment. Dendritic cells (DCs) are often termed 'nature's adjuvant' due to their exceptional capacity for initiating both innate and adaptive immune responses...
July 18, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28732046/qualitative-differences-in-cellular-immunogenicity-elicited-by-hepatitis-c-virus-t-cell-vaccines-employing-prime-boost-regimens
#5
Wendy G Tan, Iryna Zubkova, Alla Kachko, Frances Wells, Heiko Adler, Gerd Sutter, Marian E Major
T-cell based vaccines have been considered as attractive candidates for prevention of hepatitis C virus (HCV) infections. In this study we compared the magnitude and phenotypic characteristics of CD8+ T-cells induced by three commonly used viral vectors, Adenovirus-5 (Ad5), Vaccinia virus (VV) and Modified Vaccinia Ankara (MVA) expressing the HCV NS3/4A protein. C57/BL6 mice were primed with DNA expressing NS3/4A and boosted with each of the viral vectors in individual groups of mice. We then tracked the vaccine-induced CD8+ T-cell responses using pentamer binding and cytokine production analysis...
2017: PloS One
https://www.readbyqxmd.com/read/28730266/-malignant-melanoma-current-status
#6
REVIEW
J K Winkler, K Buder-Bakhaya, A Dimitrakopoulou-Strauss, A Enk, J C Hassel
CLINICAL ISSUE: The incidence of malignant melanoma is continuously increasing. The prognosis of metastatic disease is still limited. STANDARD TREATMENT: Until a few years ago palliative chemotherapy with a limited response rate was the standard treatment for metastatic melanoma. TREATMENT INNOVATIONS: Immunotherapy and targeted therapy provide new treatment options. Immune checkpoint inhibitors have significantly improved the prognosis. DIAGNOSTIC WORK-UP: Regional lymph node sonography, computed tomography (CT) of the neck, chest and abdomen and brain magnetic resonance imaging (MRI) are routinely used...
July 20, 2017: Der Radiologe
https://www.readbyqxmd.com/read/28729550/anti-tumor-activity-and-immunotherapeutic-potential-of-a-bisphosphonate-prodrug
#7
Yoshimasa Tanaka, Masashi Iwasaki, Kaoru Murata-Hirai, Kenji Matsumoto, Kosuke Hayashi, Haruki Okamura, Tomoharu Sugie, Nagahiro Minato, Craig T Morita, Masakazu Toi
Bisphosphonates have benefits in breast cancer and multiple myeloma patients and have been used with adoptive immunotherapy with γδ T cells expressing Vγ2 Vδ2 TCRs. Although treatment with γδ T cells is safe, it has shown limited efficacy. Present bisphosphonates stimulate γδ T cells but were designed to inhibit bone resorption rather than treating cancer and have limited oral absorption, tumor cell entry, and cause bone side effects. The development of phosphate and phosphonate nucleotide prodrugs has led to important drugs for hepatitis C and HIV...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28728794/myeloid-suppressor-cells-in-cancer-and-autoimmunity
#8
REVIEW
Antonio Sica, Marco Massarotti
A bottleneck for immunotherapy of cancer is the immunosuppressive microenvironment in which the tumor cells proliferate. Cancers harness the immune regulatory mechanism that prevents autoimmunity from evading immunosurveillance and promoting immune destruction. Regulatory T cells, myeloid suppressor cells, inhibitory cytokines and immune checkpoint receptors are the major components of the immune system acting in concert with cancer cells and causing the subversion of anti-tumor immunity. This redundant immunosuppressive network poses an impediment to efficacious immunotherapy by facilitating tumor progression...
July 17, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28725429/pretreatment-antigen-specific-immunity-and-regulation-association-with-subsequent-immune-response-to-anti-tumor-dna-vaccination
#9
Laura E Johnson, Brian M Olson, Douglas G McNeel
BACKGROUND: Immunotherapies have demonstrated clinical benefit for many types of cancers, however many patients do not respond, and treatment-related adverse effects can be severe. Hence many efforts are underway to identify treatment predictive biomarkers. We have reported the results of two phase I trials using a DNA vaccine encoding prostatic acid phosphatase (PAP) in patients with biochemically recurrent prostate cancer. In both trials, persistent PAP-specific Th1 immunity developed in some patients, and this was associated with favorable changes in serum PSA kinetics...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28725226/jnk-pathway-associated-phosphatase-dusp22-suppresses-cd4-t-cell-activation-and-th1-th17-cell-differentiation-and-negatively-correlates-with-clinical-activity-in-inflammatory-bowel-disease
#10
Rui Zhou, Ying Chang, Jing Liu, Min Chen, Hongling Wang, Meifang Huang, Shi Liu, Xiaobing Wang, Qiu Zhao
This study aimed to investigate the role of JNK pathway-associated phosphatase (JKAP) in inflammatory bowel disease (IBD). JKAP expression was analyzed in the intestinal mucosa of 81 IBD patients and 25 healthy controls (HCs) by qPCR and immunoblotting. The correlations of JKAP with clinical activity and inflammatory cytokines were performed. JKAP expression before and after infliximab treatment was also measured. CD4(+) T cells were isolated from peripheral blood in active IBD patient and HCs and transduced with lentivirus-encoding JKAP (LV-JKAP), anti-JKAP (LV-anti-JKAP), or empty vector (LV-scramble), and JKAP functions on IBD CD4(+) T cells were subsequently investigated...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28725030/a-practical-model-evaluating-antiviral-cytokines-by-natural-killer-cells-in-treatment-na%C3%A3-ve-patients-with-chronic-hepatitis-b-virus-infection
#11
Xiaoyan Li, Yurong Gu, Xiaobo Guo, Lin Gu, Liang Zhou, Xiaojuan Wu, Xueqin Wang, Zania Stamataki, Yuehua Huang
Natural killer (NK) cells play a major role in anti-viral immunity as first line defense during hepatitis B infection, particularly in untreated patients whose T cells functions are profoundly impaired. Cytokine interferon (IFN)-γ and tumor necrosis factor (TNF)-α produced by NK cells are important anti-viral factors. However, there is lack of a quantifiable model to evaluate cytokine responses by NK cells. In this study, almost half of the patients (47.9%) beyond treatment criteria had high cytokine activity, although it was lower than those recommended for antiviral therapy (78...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28724377/combination-therapy-for-melanoma-with-braf-mek-inhibitor-and-immune-checkpoint-inhibitor-a-mathematical-model
#12
Xiulan Lai, Avner Friedman
BACKGROUND: The B-raf gene is mutated in up to 66% of human malignant melanomas, and its protein product, BRAF kinase, is a key part of RAS-RAF-MEK-ERK (MAPK) pathway of cancer cell proliferation. BRAF-targeted therapy induces significant responses in the majority of patients, and the combination BRAF/MEK inhibitor enhances clinical efficacy, but the response to BRAF inhibitor and to BRAF/MEK inhibitor is short lived. On the other hand, treatment of melanoma with an immune checkpoint inhibitor, such as anti-PD-1, has lower response rate but the response is much more durable, lasting for years...
July 19, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/28723738/phosphatase-and-tensin-homolog-pten-is-down-regulated-in-human-nk-t-cell-lymphoma-and-corrects-with-clinical-outcomes
#13
Xiaorui Fu, Xudong Zhang, Jinli Gao, Xin Li, Lei Zhang, Ling Li, Xinhua Wang, Zhenchang Sun, Zhaoming Li, Yu Chang, Qingjiang Chen, Mingzhi Zhang
Nasal-type natural killer/T-cell (NK/T-cell) lymphoma is a more aggressive sub-group of non-Hodgkin lymphoma, which is more common in Asia. The phosphatase and tensin homolog (PTEN) was originally discovered as a candidate tumor suppressor mutated and lost in various cancers. However, its clinical value and role in NK/T-cell lymphoma remain to be further explored. In the present study, we analyzed PTEN protein expression in 60 cases of human NK/T-cell lymphoma tissues and 40 cases of control nasal mucosa tissues specimens by immunohistochemical analysis...
July 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28723659/data-driven-analysis-of-immune-infiltrate-in-a-large-cohort-of-breast-cancer-and-its-association-with-disease-progression-er-activity-and-genomic-complexity
#14
Ruth Dannenfelser, Marianne Nome, Andliena Tahiri, Josie Ursini-Siegel, Hans Kristian Moen Vollan, Vilde D Haakensen, Åslaug Helland, Bjørn Naume, Carlos Caldas, Anne-Lise Børresen-Dale, Vessela N Kristensen, Olga G Troyanskaya
The tumor microenvironment is now widely recognized for its role in tumor progression, treatment response, and clinical outcome. The intratumoral immunological landscape, in particular, has been shown to exert both pro-tumorigenic and anti-tumorigenic effects. Identifying immunologically active or silent tumors may be an important indication for administration of therapy, and detecting early infiltration patterns may uncover factors that contribute to early risk. Thus far, direct detailed studies of the cell composition of tumor infiltration have been limited; with some studies giving approximate quantifications using immunohistochemistry and other small studies obtaining detailed measurements by isolating cells from excised tumors and sorting them using flow cytometry...
July 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28723561/crosstalk-between-regulatory-t-cells-and-tumor-associated-dendritic-cells-negates-anti-tumor-immunity-in-pancreatic-cancer
#15
Jung-Eun Jang, Cristina H Hajdu, Caroline Liot, George Miller, Michael L Dustin, Dafna Bar-Sagi
Regulatory T (Treg) cell infiltration constitutes a prominent feature of pancreatic ductal adenocarcinoma (PDA). However, the immunomodulatory function of Treg cells in PDA is poorly understood. Here, we demonstrate that Treg cell ablation is sufficient to evoke effective anti-tumor immune response in early and advanced pancreatic tumorigenesis in mice. This response is dependent on interferon-γ (IFN-γ)-producing cytotoxic CD8(+) T cells. We show that Treg cells engage in extended interactions with tumor-associated CD11c(+) dendritic cells (DCs) and restrain their immunogenic function by suppressing the expression of costimulatory ligands necessary for CD8(+) T cell activation...
July 18, 2017: Cell Reports
https://www.readbyqxmd.com/read/28721731/self-assembled-injectable-peptide-hydrogels-capable-of-triggering-antitumor-immune-response
#16
Ruirui Xing, Shukun Li, Ning Zhang, Guizhi Shen, Helmuth Möhwald, Xuehai Yan
Self-assembled peptide hydrogels are particularly appealing for drug delivery, tissue engineering, and anti-tumor therapy due to various advantageous features including excellent biocompatibility and biodegradability, defined molecular and higher organized structures and easy availability. However, the poor mechanical and rheological properties of assembled peptide hydrogels cause difficulties in injection, thus limiting further applications. Herein, injectable peptide-based hydrogels with tunable mechanical and rheological properties were obtained by combination with a positively charged poly-peptide (poly-L-lysine, PLL)...
July 19, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/28720900/low-frequency-ultrasound-induced-vegf-suppression-and-synergy-with-dendritic-cell-mediated-anti-tumor-immunity-in-murine-prostate-cancer-cells-in-vitro
#17
Wei Zhang, Wen-De Shou, Yan-Jun Xu, Wen-Kun Bai, Bing Hu
High tumor vascular endothelial growth factor (VEGF) levels are associated with poor treatment outcomes in prostate cancer (PCa), and immune deficiency in the PCa microenvironment, especially suppression of dendritic cell (DC) proliferation, has been confirmed. In this study, we (1) investigated whether VEGF participates in DC suppression in murine PCa cells (RM-1), (2) down-regulated VEGF expression using low-frequency ultrasound and microbubbles (UM), and (3) further explored any synergistic effect on immunological activation...
July 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28720549/evolutionary-basis-of-a-new-approach-for-the-treatment-of-malignant-brain-tumors-from-mice-to-humans
#18
Pedro R Lowenstein, Maria G Castro
Glioma cells are one of the most aggressive and malignant tumors. Following initial surgery, and radio-chemotherapy they progress rapidly, so that patients' median survival remains under two years. They invade throughout the brain, which makes them difficult to treat, and are universally lethal. Though total resection is always attempted it is not curative. Standard of care in 2016 comprises surgical resection, radiotherapy and chemotherapy (temozolomide). Median survival is currently ~14-20months post-diagnosis though it can be higher in high complexity medical university centers, or during clinical trials...
July 15, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28719632/viscum-album-neutralizes-tumor-induced-immunosuppression-in-a-human-in-vitro-cell-model
#19
Carmen Steinborn, Amy Marisa Klemd, Ann-Sophie Sanchez-Campillo, Sophie Rieger, Marieke Scheffen, Barbara Sauer, Manuel Garcia-Käufer, Konrad Urech, Marie Follo, Annekathrin Ücker, Gunver Sophia Kienle, Roman Huber, Carsten Gründemann
Tumor cells have the capacity to secrete immunosuppressive substances in order to diminish dendritic cell (DC) activity and thereby escape from immune responses. The impact of mistletoe (Viscum album) extracts (VAE), which are frequently used as an additive anti-cancer therapy to stimulate the immune response, is still unknown. Using a human cellular system, the impact of two different VAE (VAEA + VAEI) on the maturation of human dendritic cells and on T cell function has been investigated using flow cytometry, automated fluorescence microscopy and cytokine bead array assays...
2017: PloS One
https://www.readbyqxmd.com/read/28716484/the-anti-tumor-activity-of-the-stat3-inhibitor-stx-0119-occurs-via-promotion-of-tumor-infiltrating-lymphocyte-accumulation-in-temozolomide-resistant-glioblastoma-cell-line
#20
Yasuto Akiyama, Chizu Nonomura, Tadashi Ashizawa, Akira Iizuka, Ryota Kondou, Haruo Miyata, Takashi Sugino, Koichi Mitsuya, Nakamasa Hayashi, Yoko Nakasu, Akira Asai, Mamoru Ito, Yoshio Kiyohara, Ken Yamaguchi
STAT3 is considered to be a key molecule to mediating tumor-induced immunosuppression in various manners at tumor sites, by acting through immune-regulatory cytokines derived from the tumor cells. Specific anti-STAT3 inhibitors have been developed using nude mouse models transplanted with human tumor cells. However, mouse systems cannot accurately represent the human immune response induced by STAT3 inhibitors, and more humanized therapeutic model based on human immune cells and tumors are needed. In the present study, an immune-deficient NOG mouse with the deletion of both MHC-class I and class II genes, an MHC-double knockout mouse (dKO-NOG), was developed and used to establish humanized immunotherapeutic model...
July 14, 2017: Immunology Letters
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