CD8+CD28- T regulatory lymphocytes inhibiting T cell proliferative and cytotoxic functions infiltrate human cancers
CD8+CD28- T regulatory lymphocytes inhibiting T cell proliferative and cytotoxic functions infiltrate human cancers
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DOI：
10.4049/jimmunol.179.7.4323
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发表时间：
2007-10-01
影响因子：
4.4
通讯作者：
Indiveri, Francesco
中科院分区：
文献类型：
--
作者：
Filaci, Gilberto;Fenoglio, Daniela;Indiveri, Francesco
肿瘤生长是由于其逃避免疫系统监视的能力。肿瘤浸润调节淋巴细胞可能在决定肿瘤逃避免疫控制方面发挥重要作用。本研究旨在表征浸润人类癌症的 CD8(+)CD28(-) T 调节细胞的表型和功能。通过抑制测定对来自 42 种人类癌症的原始肿瘤病变和/或卫星淋巴结浸润的淋巴细胞进行表型研究和功能分析。前所未有的观察发现，CD8(+)CD28(-) T 调节性淋巴细胞几乎持续存在于人类肿瘤中并发挥作用，能够抑制 T 细胞增殖和细胞毒性。 CD4(+)CD25(+) T 调节性淋巴细胞与 CD8(+)CD28(-) T 调节性细胞结合，因此综合考虑，肿瘤浸润性调节性 T 细胞亚群的免疫抑制活性可能占主导地位。调节性 T 细胞的浸润似乎与肿瘤相关，存在于转移性卫星淋巴结中，但不存在于无转移性卫星淋巴结中；它可能取决于原位生成（通过细胞因子产生）和外周招募（通过趋化因子分泌）。总的来说，这些结果对癌症免疫治疗具有致病相关性和意义。
Tumor growth is allowed by its ability to escape immune system surveillance. An important role in determining tumor evasion from immune control might be played by tumor-infiltrating regulatory lymphocytes. This study was aimed at characterizing phenotype and function of CD8(+)CD28(-) T regulatory cells infiltrating human cancer. Lymphocytes infiltrating primitive tumor lesion and/or satellite lymph node from a series of 42 human cancers were phenotypically studied and functionally analyzed by suppressor assays. The unprecedented observation was made that CD8(+)CD28(-) T regulatory lymphocytes are almost constantly present and functional in human tumors, being able to inhibit both T cell proliferation and cytotoxicity. CD4(+)CD25(+) T regulatory lymphocytes associate with CD8(+)CD28(-) T regulatory cells so that the immunosuppressive activity of tumor-infiltrating regulatory T cell subsets, altogether considered, may become predominant. The infiltration of regulatory T cells seems tumor related, being present in metastatic but not in metastasis-free satellite lymph nodes; it likely depends on both in situ generation (via cytokine production) and recruitment from the periphery (via chemokine secretion). Collectively, these results have pathogenic relevance and implication for immunotherapy of cancer.