Tumor-infiltrating CD4(+) T cells in patients with gastric cancer.

Tumor-infiltrating CD4(+) T cells in patients with gastric cancer.
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DOI:
10.1186/s12935-017-0489-4
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发表时间:
2017
影响因子:
5.8
通讯作者:
Gao Q
Gao Q
中科院分区:
医学2区
文献类型:
--
作者:
Yuan L;Xu B;Yuan P;Zhou J;Qin P;Han L;Chen G;Wang Z;Run Z;Zhao P;Gao Q

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T淋巴细胞在清除病毒和肿瘤抗原中起着不可或缺的重要作用。在胃癌(GC)存在的情况下,抑制分子与细胞因子对肿瘤浸润的CD 4 + T细胞的影响知之甚少。本研究探讨胃癌患者外周血及组织中肿瘤浸润T细胞亚群的分布、分化及抑制表型。2014年至2015年,在中国郑州大学附属肿瘤医院招募了根据术前分期和剖腹探查结果诊断为GC的患者。基于肿瘤浸润淋巴细胞的分离和细胞内IFN-γ染色测定进行表型分析。进行统计分析以显示显著性。结果表明,肿瘤组织中CD_4 ~+ T细胞占CD_3 ~+细胞的比例明显高于癌旁组织。胃癌患者肿瘤浸润T细胞上的CD 4 + CD 25 highCD 127 lowregulatory T细胞(Tcells,Tcells)、PD-1+、Tim-3+和PD-1+ Tim-3+细胞的表达较相应外周血和瘤周T细胞上的表达上调。阻断PD-1+和Tim-3+可有效恢复肿瘤浸润性T细胞产生干扰素-γ(IFN-γ)。PD-1+和Tim-3+联合抑制对CD 4 + T细胞分泌IFN-γ具有协同作用。结果表明,在评价抗肿瘤免疫治疗时,应考虑免疫浸润的组成、抑制剂和位置。为T细胞功能障碍的机制提供了新的见解。本文的在线版本(10.1186/s12935-017-0489-4)包含补充材料,可供授权用户使用。
T lymphocytes play an indispensably important role in clearing virus and tumor antigen. There is little knowledge about impacts of inhibitory molecules with cytokine on tumor-infiltrating CD4+ T-cells in the presence of gastric cancer (GC). This study investigated the distribution of tumor-infiltrating T-cells subset and the differentiation as well as inhibitory phenotype of T-cells from blood and tissues of GC patients. Patients with GC diagnosed on the basis of pre-operative staging and laparotomy findings were approached for enrollment between 2014 and 2015 at the Affiliated Cancer Hospital of Zhengzhou University, China. Phenotypic analysis based on isolation of tumor-infiltrating lymphocytes and intracellular IFN-γ staining assay is conducted. Statistical analysis is performed to show significance. The results showed that the percentage of CD4+ T-cells among CD3+ cells in tumors was significantly higher than that in the matched paraneoplastic tissue. CD4+ CD25high CD127low regulatory T-cells (Tregs), PD-1+, Tim-3+, and PD-1+ Tim-3+ cells were up-regulated on tumor infiltrating T-cells from patients with GC compared to their expressions on corresponding peripheral blood and peritumoral T-cells. Blockades of PD-1+ and Tim-3+ were effective in restoring tumor infiltrating T-cells’ production of interferon-gamma (IFN-γ). Combined PD-1+ and Tim-3+ inhibition had a synergistic effect on IFN-γ secretion by CD4+ T-cells. The results suggested that the composition, inhibitors, and location of the immune infiltrate should be considered when evaluating antitumor immunotherapy. A new insight into the mechanisms underlying T cell dysfunction is provided. The online version of this article (10.1186/s12935-017-0489-4) contains supplementary material, which is available to authorized users.
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