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Activated cytotoxic lymphocytes promote tumor progression by increasing the ability of 3LL tumor cells to mediate MDSC chemoattraction via Fas signaling

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Cellular & Molecular Immunology 2015年第1期12卷 66-76页

作者： Fei Yang Yinxiang Wei Zhijian Cai Lei Yu Lingling Jiang Chengyan Zhang Huanmiao Yan Qingqing Wang Xuetao Cao Tingbo Liang Jianli Wang Institute of Immunology Zhejiang University School of Medicine Hangzhou China The Second Affiliated Hospital Hangzhou Zhejiang China Institute of Immunology and National Key Laboratory of Medical Immunology Second Military Medical University Shanghai China

The Fas/FasL system transmits intracellular apoptotic signaling, inducing cell apoptosis. However, Fas signaling also exerts non-apoptotic functions in addition to inducing tumor cell apoptosis. For example, Fas signaling induces lung cancer tumor cells to produce prostaglandin E2 （PGE2） and recruit myeloid-derived suppressor cells （MDSCs）. Activated cytotoxic T lymphocytes （CTLs） induce and express high levels of FasL, but the effects of Fas activation initiated by FasL in CTLs on apoptosis-resistant tumor cells remain largely unclear. We purified activated CD8^＋ T cells from OT-1 mice, evaluated the regulatory effects of Fas activation on tumor cell escape and investigated the relevant mechanisms. We found that CTLs induced tumor cells to secrete PGE2 and increase tumor cell-mediated chemoattraction of MDSCs via Fas signaling, which was favorable to tumor growth. Our results indicate that CTLs may participate in the tumor immune evasion process. To the best of our knowledge, this is a novel mechanism by which CTLs play a role in tumor escape. Our findings implicate a strategy to enhance the antitumor immune response via reduction of negative immune responses to tumors promoted by CTLs through Fas signaling.

关键词： activated cytotoxic T lymphocytes Fas/FasL myeloid-derived suppressor cells prostaglandin E2 tumor escape

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Colon cancer and the immune system:The role of tumor invading T cells

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World Journal of Gastroenterology 2006年第45期12卷 7233-7238页

作者： Maximilian Waldner Carl C Schimanski Markus F Neurath I. Department of Medicine University of Mainz Mainz Germany

Colon cancer is still one of the leading causes of cancer death worldwide. Although the host immune system has been shown to react against tumor cells, mainly through tumor infi ltrating lymphocytes and NK cells, tumor cells may utilize different ways to escape anti-tumor immune response. tumor infi ltration of CD8+ and CD4+ (T-bet+) effector T cells has been attributed to a beneficial outcome, and the enhancement of T cell activation through T cell receptor stimulation and co-stimulatory signals provides promising strategies for immunotherapy of colon cancer. Growing evidence supports a role for the Fas/FasL system in tumor immunology, although the mechanisms and consequences of FasL activation in colon cancer are not completely understood. In animal models, depletion of regulatory T cells (CD4+ CD25+ T cells) can enhance the anti-tumor immune response under certain conditions. Taken together, recent insights in the immune reaction against colon carcinoma have provided new approaches to immunotherapy, although much remains to be learned about the exact mechanisms.

关键词： CD4-positive T-lymphocytes CD8-positive T-lymphocytes Immunology Colonic neoplasms therapy Colorectal neoplasms Humans Lymphocytes tumor-infiltrating tumor escape

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Roles of Tregs in development of hepatocellular carcinoma:A meta-analysis

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World Journal of Gastroenterology 2014年第24期20卷 7971-7978页

作者： Hong-Qiang Zhao Wei-Min Li Zhong-Qiou Lu Yong-Ming Yao Medical School of Chinese People’s Liberation Army Department of Hepatobiliary Surgery the 309~(th) Hospital of Chinese People’s Liberation Army Department of Emergency Care First Affiliated Hospital of Wenzhou Medical College Burns Institute First Hospital Affiliated to the Chinese PLA General Hospital

AIM: To assess systematically the association between regulatory T cells (Tregs) and hepatocellular carcinoma (HCC).

关键词： Hepatocellular carcinoma Regulatory T cells Meta-analysis tumor escape Cellular immunity

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Immune escape mechanism of hepatocellular carcinoma cells via trogocytosis of HLA-G

Immune escape mechanism of hepatocellular carcinoma cells vi...

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浙江省免疫学会第六次会员代表大会暨第十一次学术大会

作者： Hu Bin Lin Ai-fen Yan Wei-hua Medical Research Center Taizhou Hospital of Zhejiang Province

Objective HLA-G is an important immune tolerant molecule in vivo which is closely related to malignant *** inducing expression of HLA-G has been observed in hepatocellular carcinoma,which can directly inhibiting the immunological function of immune effector cells by binding to inhibitory receptors or involves in immune regulation process by inducing T regulatory cells to induce organism tolerance and promote immune escape of tumor ***2 cells don’t express HLA-G1 antigen and co-culture with HepG2 cells expressing HLA-G1(HepG2-G1).HLA-G1 negative HepG2 cells can be detected to express HLA-G1 to investigate the mechanism of acquisition of HLA-G1 *** mRNA and protein of HLA-G can be found in the human hepatocellular cell ***2 cells express HLA-G1 could make more HepG2 cells express HLA-G1 via this way,so that it plays a potential role in immune *** HepG2 cells stably expressing HLA-G1(HepG2-G1)were ***2 cells were co-cultured with HepG2-G1 cells which was pre-labeled with lipophilic dye PKH67 to observe the acquisition of HLA-G by HepG2 cells evaluated by flow cytometry and fluorescence *** HepG2 cells could acquire HLA-G1 from HepG2-G1 cells via intercellular contact:trogocytosis.

关键词： HLA-G1 HepG2 cells trogocytosis tumor escape

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Analysis of regulatory T cells frequency in peripheral blood and tumor tissues in papillary thyroid carcinoma with and without Hashimoto’s thyroiditis

Analysis of regulatory T cells frequency in peripheral blood...

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2014第六届全国甲状腺肿瘤学术大会

作者： Xinwei Yun Youzhong Liu Ming Gao Yang Yu Xiaolong Li Department of Head ＆ Neck tumor Key Laboratory of Cancer Prevention and Therapy Tianjin Medical University Cancer Institute ＆ Hospital National Clinical Research Center of Cancer

Purpose: Regulatory T cells（Treg） suppress the immune reaction. The aim of the present study was to investigate the clinicopathologic significance and roles of Treg in Papillary thyroid carcinoma（PTC） patients with and without Hashimoto’s thyroiditis. Methods: Flow cytometry was used to detect percentage of CD4+CD25+CD127low/-Treg among CD4+ T cells in peripheral blood. Foxp3+ Treg were detected by immunohistochemistry in the tumor tissues. Results: The percentage of CD4+CD25+CD127low/- Treg among CD4+ T cells was significantly higher in PTC patients than that in thyroid nodular goiter（TNG） patients. There were large numbers of tumor-infiltrating Foxp3+ Treg in primary PTC and metastasis lymph nodes tissues, however, there was no Foxp3 expression in the TNG tissues. Higher percentage of Treg both in peripheral blood and tumor tissues was associated with extrathyroidal extension and lymph nodes metastasis. The percentage of CD4+CD25+CD127low/- Treg among CD4+ T cells in peripheral blood of PTC patients with Hashimoto’s thyroiditis（HT） was significantly lower, whereas the infiltration of Foxp3+ Treg in tissues of PTC with HT tended to be increased. Conclusions: We concluded that the prevalence of Treg increased in peripheral blood as well as in the tumor tissues of PTC patients compared with that of TNG patients. The high prevalence of Treg was associated with aggressiveness. There may be a compensatory expansion of Treg at the sites of inflammation in tissues of PTC with HT contributing the immune response suppression.

关键词： Papillary thyroid carcinoma Regulatory T cells tumor escape Hashimoto’s thyroiditis tumor microenvironment

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