Alteration of CD4 T cell subsets in metastatic lymph nodes of human gastric cancer

Alteration of CD4 T cell subsets in metastatic lymph nodes of human gastric cancer
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DOI:
10.3892/or.2015.4064
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发表时间:
2015-08-01
期刊:
影响因子:
4.2
通讯作者:
Hirakawa, Kosei
Hirakawa, Kosei
中科院分区:
医学3区
文献类型:
--
作者:
Okita, Yoshihiro;Ohira, Masaichi;Hirakawa, Kosei

文献摘要

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对肿瘤浸润免疫细胞的研究表明,免疫逃逸在肿瘤生长中起重要作用。本研究的目的是研究转移对人类临床样本中CD 4(+)T细胞亚群的影响。通过流式细胞术、qRT-PCR和免疫组织化学评估源自肿瘤引流淋巴结(TDLN)和原发性癌症标本的单细胞悬液。在TDLN中检测到的CD 4(+)T细胞亚群中,效应T细胞(TO)在转移性TDLN(mTDLN)中。显著低于无转移TDLN(mfTDLN)。与正常对照组相比,mfTDLN组的T-E增加。类似地,mTDLN中的效应记忆T细胞(T)显著低于对照和mfTDLN。T-EM在TDLN中的比例与肿瘤浸润的CD 4(+)和CD 8(+)T细胞数量呈显著正相关。在mTDLN中Thl与Th 2的比率较低,并且在mTDLN中Treg显著高于mfTDLN。TDLN中CD 4(+)T细胞和T-E亚群受到转移的显着影响。免疫抑制细胞表现出向TDLN的迁移增加,其中CD 4(+)T-E的子集在肿瘤微环境中偏向免疫耐受。
Studies of tumor-infiltrating immune cells have revealed that immune escape plays an important role in tumor growth. The aim of the present study was to investigate the impact of metastasis affecting CD4(+) T cell subsets in human clinical samples. Single-cell suspensions derived from tumor-draining lymph node (TDLN) and primary cancer specimens were assessed by flow cytometry, qRT-PCR and immunohistochemistry. In the CD4(+) T cell subsets detected in TDLN, effector T cells (TO in metastatic TDLN (mTDLN). was significantly lower than that in metastatic-free TDLN (mfTDLN). T-E in mfTDLN were increased compared with normal controls. Similarly, effector memory T cells (T) in mTDLN was significantly lower than in control and mfTDLN. There was a significantly positive correlation between the proportion of T-EM in TDLN and number of tumor-infiltrating CD4(+) and CD8(+) T cells. Thl to Th2 ratio was lower in mTDLN, and Treg in mTDLN was significantly higher than in mfTDLN. CD4(+) T cell and T-E subsets in TDLN were significantly affected by metastasis. Immunosuppressive cells exhibit increased migration to TDLN, in which a subset of CD4(+) T-E is skewed towards immune tolerance in the tumor microenvironment.