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Tumor infiltrating lymphocyte

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https://www.readbyqxmd.com/read/28929191/overview-of-lag-3-expressing-il-10-producing-regulatory-t-cells
#1
Keishi Fujio, Kazuhiko Yamamoto, Tomohisa Okamura
Regulatory T cells (Treg cells) play crucial roles in the induction of peripheral tolerance to self- and foreign-antigens. IL-10-producing regulatory T cells (IL-10-producing Treg cells) constitute a Treg cell subset characterized by the production of high amounts of IL-10, cytokine-mediated immunosuppressive capabilities, and independence of Foxp3 expression for their suppressive activity. In the past decade, identifying naturally occurring IL-10-producing Treg cells was difficult due to the lack of suitable surface markers...
September 20, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28928458/agonist-immunotherapy-restores-t-cell-function-following-mek-inhibition-improving-efficacy-in-breast-cancer
#2
Sathana Dushyanthen, Zhi Ling Teo, Franco Caramia, Peter Savas, Christopher P Mintoff, Balaji Virassamy, Melissa A Henderson, Stephen J Luen, Mariam Mansour, Michael H Kershaw, Joseph A Trapani, Paul J Neeson, Roberto Salgado, Grant A McArthur, Justin M Balko, Paul A Beavis, Phillip K Darcy, Sherene Loi
The presence of tumor-infiltrating lymphocytes in triple-negative breast cancers is correlated with improved outcomes. Ras/MAPK pathway activation is associated with significantly lower levels of tumor-infiltrating lymphocytes in triple-negative breast cancers and while MEK inhibition can promote recruitment of tumor-infiltrating lymphocytes to the tumor, here we show that MEK inhibition adversely affects early onset T-cell effector function. We show that α-4-1BB and α-OX-40 T-cell agonist antibodies can rescue the adverse effects of MEK inhibition on T cells in both mouse and human T cells, which results in augmented anti-tumor effects in vivo...
September 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28928380/predictors-of-responses-to-immune-checkpoint-blockade-in-advanced-melanoma
#3
N Jacquelot, M P Roberti, D P Enot, S Rusakiewicz, N Ternès, S Jegou, D M Woods, A L Sodré, M Hansen, Y Meirow, M Sade-Feldman, A Burra, S S Kwek, C Flament, M Messaoudene, C P M Duong, L Chen, B S Kwon, A C Anderson, V K Kuchroo, B Weide, F Aubin, C Borg, S Dalle, O Beatrix, M Ayyoub, B Balme, G Tomasic, A M Di Giacomo, M Maio, D Schadendorf, I Melero, B Dréno, A Khammari, R Dummer, M Levesque, Y Koguchi, L Fong, M Lotem, M Baniyash, H Schmidt, I M Svane, G Kroemer, A Marabelle, S Michiels, A Cavalcanti, M J Smyth, J S Weber, A M Eggermont, L Zitvogel
Immune checkpoint blockers (ICB) have become pivotal therapies in the clinical armamentarium against metastatic melanoma (MMel). Given the frequency of immune related adverse events and increasing use of ICB, predictors of response to CTLA-4 and/or PD-1 blockade represent unmet clinical needs. Using a systems biology-based approach to an assessment of 779 paired blood and tumor markers in 37 stage III MMel patients, we analyzed association between blood immune parameters and the functional immune reactivity of tumor-infiltrating cells after ex vivo exposure to ICB...
September 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28928158/characterization-of-the-immune-microenvironment-in-hepatocellular-carcinoma-hcc
#4
Mark Yarchoan, Dongmei Xing, Lan Luan, Haiying Xu, Rajni Sharma, Aleksandra Popovic, Timothy M Pawlik, Amy K Kim, Qingfeng Zhu, Elizabeth M Jaffee, Janis Taube, Robert A Anders
PURPOSE: Hepatocellular carcinoma (HCC) often arises in the setting of chronic liver inflammation and may be responsive to novel immunotherapies. EXPERIMENTAL DESIGN: To characterize the immune microenvironment in HCC, immunohistochemical (IHC) staining was performed for CD8 positive T lymphocytes, PD-1 positive and LAG-3 positive lymphocytes, CD163 positive macrophages, and PD-L1 expression in tumor and liver background from 29 cases of resected HCC. RESULTS: Expression of CD8 was reduced in tumor and expression of CD163 was reduced at the tumor interface...
September 19, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28927159/diagnostic-value-of-inflammatory-cell-infiltrates-tumor-stroma-percentage-and-disease-free-survival-in-patients-with-colorectal-cancer
#5
Katarzyna Jakubowska, Wojciech Kisielewski, Luiza Kańczuga-Koda, Mariusz Koda, Waldemar Famulski
The anticancer immune defense mechanism involves humoral and cellular responses. The main effector mechanisms of antitumor responses involve the following: the activity of cytotoxic T cells; the activation of macrophages and neutrophils; the activity of cytokines secreted by T cells; and natural killer cell activity. Selected cell populations are responsible for the stimulation or suppression of the immune system against tumor cells. Therefore, the aim of the present study was to evaluate the location, extent and composition of the cellular inflammatory infiltration of tumors in patients with colorectal cancer (CRC)...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28927136/low-risk-population-among-patients-with-tumor-node-metastasis-stage-iii-iv-oral-squamous-cell-carcinoma
#6
Tohru Ikeda, Sachiko Seki, Mutsunori Fujiwara, Masaaki Matsuura, Yuu Ozaki-Honda, Shuichi Fujita, Hisazumi Ikeda, Masahiro Umeda, Izumi Asahina
A novel system auxiliary to the Union for International Cancer Control classification may allow the prognosis of patients with malignant tumors at similar stages to be predicted, as currently this is challenging. The present study generated a novel system to predict populations at low risk among patients with stage III/IV oral squamous cell carcinoma (OSCC). A total of 41 patients who were diagnosed at stages III/IV OSCC and underwent surgical tumor resection were analyzed. Band-like or follicular lymphocyte infiltration, intraepithelial micro-abscess formation and natural killer (NK) cell infiltration were histopathologically evaluated...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28926365/primary-cutaneous-diffuse-large-b-cell-lymphoma-leg-type-with-spontaneous-regression-after-biopsy
#7
Gabriel Marrero-Alemán, Társila Montenegro-Dámaso, Yeray Peñate
Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT) represents approximately 20% of cutaneous B lymphomas with an intermediate prognosis. Spontaneous regression is uncommon; there are only 2 published cases. An 83-year-old woman presented 2 orange erythematous nodules on the back of her right leg with an elastic consistency, infiltrated, painful to the touch, and of an 8-month evolution. A histological examination revealed a dense cellular dermo-hypodermic infiltrate sparing the papillary dermis, composed of large cells with immunoblast and centroblast morphology and frequent mitosis...
October 2017: American Journal of Dermatopathology
https://www.readbyqxmd.com/read/28924054/immunosurveillance-and-immunoediting-of-breast-cancer-via-class-i-mhc-receptors
#8
Megan M Tu, Mir Munir A Rahim, Celine Sayed, Ahmad Bakur Mahmoud, Andrew P Makrigiannis
Ly49 receptors, which recognize 'self' class I major histocompatibility complex (MHC-I) molecules, enable natural killer (NK) cells to detect loss of MHC-I expression on transformed and virally-infected cells. The impact of NK cell-mediated MHC-I surveillance on immunoediting of breast cancer is still not fully understood. This work assesses the impact of Ly49 receptors on tumor development in terms of cancer control and in driving immune-evading cancer mutations. Genetically modified Ly49-deficient mice and those lacking NK cells through antibody depletion were less able to control E0771-derived mammary tumors in an MHC-I-dependent fashion...
September 18, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28923424/depletion-of-regulatory-t-cells-by-anti-icos-antibody-enhances-anti-tumor-immunity-of-tumor-cell-vaccine-in-prostate-cancer
#9
Lijun Mo, Qianmei Chen, Xinji Zhang, Xiaojun Shi, Lili Wei, Dianpeng Zheng, Hongwei Li, Jimin Gao, Jinlong Li, Zhiming Hu
ICOS(+)Treg cells exert important immunosuppressive effects in tumor immunity. We adopt a combination approach of ICOS(+)Treg cells depletion with tumor cell vaccine to evaluate anti-tumor immunity in mouse prostate cancer model. Streptavidin (SA)-mGM-CSF surface-modified RM-1 cells were prepared as the vaccine and the mouse subcutaneous prostate tumor model was used to evaluate the immunity. Tumor growth, flow cytometry, immunohistochemistry, immunofluorescence and enzyme linked immunosorbent assay (ELISA) were performed to evaluate the therapeutic effects...
September 15, 2017: Vaccine
https://www.readbyqxmd.com/read/28922790/the-balance-between-cytotoxic-t-cell-lymphocytes-and-immune-checkpoint-expression-in-the-prognosis-of-colon-tumors
#10
Laetitia Marisa, Magali Svrcek, Ada Collura, Etienne Becht, Pascale Cervera, Kristell Wanherdrick, Olivier Buhard, Anastasia Goloudina, Vincent Jonchère, Janick Selves, Gerard Milano, Dominique Guenot, Romain Cohen, Chrystelle Colas, Pierre Laurent-Puig, Sylviane Olschwang, Jérémie H Lefèvre, Yann Parc, Valérie Boige, Côme Lepage, Thierry André, Jean-François Fléjou, Valentin Dérangère, François Ghiringhelli, Aurélien de Reynies, Alex Duval
Background: Immune checkpoint (ICK) expression might represent a surrogate measure of tumor-infiltrating T cell (CTL) exhaustion and therefore be a more accurate prognostic biomarker for colorectal cancer (CRC) patients than CTL enumeration as measured by the Immunoscore. Methods: The expression of ICKs, Th1, CTLs, cytotoxicity-related genes, and metagenes, including Immunoscore-like metagenes, were evaluated in three independent cohorts of CRC samples (260 microsatellite instable [MSI], 971 non-MSI)...
January 1, 2018: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28922374/fractional-laser-exposure-induces-neutrophil-infiltration-n1-phenotype-into-the-tumor-and-stimulates-systemic-anti-tumor-immune-response
#11
Masayoshi Kawakubo, Shadmehr Demehri, Dieter Manstein
BACKGROUND: Ablative fractional photothermolysis (aFP) using a CO2 laser generates multiple small diameter tissue lesions within the irradiation field. aFP is commonly used for a wide variety of dermatological indications, including treatment of photodamaged skin and dyschromia, drug delivery and modification of scars due to acne, surgical procedures and burns. In this study we explore the utility of aFP for treating oncological indications, including induction of local tumor regression and inducing anti-tumor immunity, which is in marked contrast to current indications of aFP...
2017: PloS One
https://www.readbyqxmd.com/read/28921877/analysis-of-infantile-fibrosarcoma-reveals-extensive-t-cell-responses-within-tumors-implications-for-immunotherapy
#12
Hua Zhu, Song Gu, Minzhi Yin, Min Shi, Chao Xin, Jianmin Zhu, Jing Wang, Siqi Huang, Chenjie Xie, Jing Ma, Ci Pan, Jingyan Tang, Min Xu, Xue-Feng Bai
BACKGROUND: Infantile fibrosarcoma (IFS) is a rare pediatric malignancy with relatively good prognosis, but the risk of progression or recurrence after therapy exists. To understand the immune microenvironment of IFS and determine if immunotherapy is a potential treatment, we analyzed T-cell responses in IFS tumors. PROCEDURE: IFS tumors were analyzed by immunohistochemistry and multicolor flow cytometry to characterize immune cell infiltration and function. Tumor infiltrating lymphocytes (TILs) were expanded in vitro and evaluated for recognition of autologous tumor cells...
September 17, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28918459/hla-class-i-expression-predicts-prognosis-and-therapeutic-benefits-from-tyrosine-kinase-inhibitors-in-metastatic-renal-cell-carcinoma-patients
#13
Jiajun Wang, Li Liu, Yang Qu, Wei Xi, Yu Xia, Qi Bai, Ying Xiong, Qilai Long, Jiejie Xu, Jianming Guo
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...
September 16, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28915695/evaluation-of-intracavitary-administration-of-curcumin-for-the-treatment-of-sarcomatoid-mesothelioma
#14
Daniel L Pouliquen, Béatrice Nawrocki-Raby, Joëlle Nader, Stéphanie Blandin, Myriam Robard, Philippe Birembaut, Marc Grégoire
A rat model of sarcomatoid mesothelioma, mimicking some of the worst clinical conditions encountered, was established to evaluate the therapeutic potential of intracavitary curcumin administration. The M5-T1 cell line, selected from a collection established from F344 rats induced with asbestos, produces tumors within three weeks, with extended metastasis in normal tissues, after intraperitoneal inoculation in syngeneic rats. The optimal concentration/time conditions for killing M5-T1 cells with curcumin were first determined in vitro...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915679/prognostic-role-of-tumor-infiltrating-lymphocytes-in-gastric-cancer-a-meta-analysis
#15
Xiao Zheng, Xing Song, Yingjie Shao, Bin Xu, Lujun Chen, Qi Zhou, Wenwei Hu, Dachuan Zhang, Changping Wu, Min Tao, Yibei Zhu, Jingting Jiang
BACKGROUND: In patients with gastric cancer, the prognostic value of tumor-infiltrating lymphocytes (TILs) is still controversial. A meta-analysis was performed to evaluate the prognostic value of TILs in gastric cancer. MATERIALS AND METHODS: We identify studies from PubMed, Embase and the Cochrane Library to assess the prognostic effect of TILs in patients with gastric cancer. Fixed-effects models or random-effects models were used estimate the pooled hazard ratios (HRs) for overall survival (OS) and disease-free survival (DFS), which depend on the heterogeneity...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915659/data-driven-analysis-of-immune-infiltrate-in-a-large-cohort-of-breast-cancer-and-its-association-with-disease-progression-er-activity-and-genomic-complexity
#16
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...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915590/combination-of-desi2-and-ip10-gene-therapy-significantly-improves-therapeutic-efficacy-against-murine-carcinoma
#17
Chao Lin, HuaYing Yan, Jun Yang, Lei Li, Mei Tang, Xinyu Zhao, Chunlai Nie, Na Luo, Yuquan Wei, Zhu Yuan
DESI2 (also known as PNAS-4) is a novel pro-apoptotic gene activated during the early response to DNA damage. We previously reported that overexpression of DESI2 induces S phase arrest and apoptosis by activating checkpoint kinases. The present study was designed to test whether combination of DESI2 and IP10 could improve the therapy efficacy in vitro and in vivo. The recombinant plasmid co-expressing DESI2 and IP10 was encapsulated with DOTAP/Cholesterol nanoparticle. Immunocompetent mice bearing CT26 colon carcinoma and LL2 lung cancer were treated with the complex...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915554/resistance-to-ctla-4-checkpoint-inhibition-reversed-through-selective-elimination-of-granulocytic-myeloid-cells
#18
Paul E Clavijo, Ellen C Moore, Jianhong Chen, Ruth J Davis, Jay Friedman, Young Kim, Carter Van Waes, Zhong Chen, Clint T Allen
PURPOSE: Local immunosuppression remains a critical problem that limits clinically meaningful response to checkpoint inhibition in patients with head and neck cancer. Here, we assessed the impact of MDSC elimination on responses to CTLA-4 checkpoint inhibition. EXPERIMENTAL DESIGN: Murine syngeneic carcinoma immune infiltrates were characterized by flow cytometry. Granulocytic MDSCs (gMDSCs) were depleted and T-lymphocyte antigen-specific responses were measured...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28913760/impact-of-histopathology-tumor-infiltrating-lymphocytes-and-adjuvant-chemotherapy-on-prognosis-of-triple-negative-breast-cancer
#19
Roberto A Leon-Ferre, Mei-Yin Polley, Heshan Liu, Judith A Gilbert, Victoria Cafourek, David W Hillman, Ahmed Elkhanany, Margaret Akinhanmi, Jenna Lilyquist, Abigail Thomas, Vivian Negron, Judy C Boughey, Minetta C Liu, James N Ingle, Krishna R Kalari, Fergus J Couch, Daniel W Visscher, Matthew P Goetz
BACKGROUND: Given its high recurrence risk, guidelines recommend systemic therapy for most patients with early-stage triple-negative breast cancer (TNBC). While some clinicopathologic factors and tumor-infiltrating lymphocytes (TILs) are known to be prognostic in patients receiving chemotherapy, their prognostic implications in systemically untreated patients remain unknown. METHODS: From a cohort of 9982 women with surgically treated non-metastatic breast cancer, all patients with clinically reported ER-negative/borderline (≤10%) disease were selected for central assessment of ER/PR/HER2, histopathology, Ki-67, and TILs...
September 14, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28913723/therapeutic-implications-of-the-molecular-and-immune-landscape-of-triple-negative-breast-cancer
#20
REVIEW
Ana C Gregório, Manuela Lacerda, Paulo Figueiredo, Sérgio Simões, Sérgio Dias, João Nuno Moreira
Treatment and management of breast cancer imposes a heavy burden on public health care, and incidence rates continue to increase. Breast cancer is the most common female neoplasia and primary cause of death among women worldwide. The recognition of breast cancer as a complex and heterogeneous disease, comprising different molecular entities, was a landmark in our understanding of this malignancy. Valuing the impact of the molecular characteristics on tumor behavior enabled a better assessment of a patient's prognosis and increased the predictive power to therapeutic response and clinical outcome...
September 14, 2017: Pathology Oncology Research: POR
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