Filaci Gilberto, Fenoglio Daniela, Fravega Marco, Ansaldo Gianluca, Borgonovo Giacomo, Traverso Paolo, Villaggio Barbara, Ferrera Alessandra, Kunkl Annalisa, Rizzi Marta, Ferrera Francesca, Balestra Piercesare, Ghio Massimo, Contini Paola, Setti Maurizio, Olive Daniel, Azzarone Bruno, Carmignani Giorgio, Ravetti Jean Louis, Torre Giancarlo, Indiveri Francesco
Centre of Excellence for Biomedical Research, University of Genoa, Genoa, Italy.
J Immunol. 2007 Oct 1;179(7):4323-34. doi: 10.4049/jimmunol.179.7.4323.
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.
肿瘤能够逃避免疫系统的监视，从而得以生长。肿瘤浸润性调节淋巴细胞在决定肿瘤逃避免疫控制方面可能发挥重要作用。本研究旨在表征浸润人类癌症的CD8+ CD28-调节性T细胞的表型和功能。对来自42例人类癌症的原发性肿瘤病灶和/或卫星淋巴结中的浸润淋巴细胞进行了表型研究，并通过抑制试验进行了功能分析。有一个前所未有的发现，即CD8+ CD28-调节性淋巴细胞几乎始终存在于人类肿瘤中并发挥功能，能够抑制T细胞增殖和细胞毒性。CD4+ CD25+调节性淋巴细胞与CD8+ CD28-调节性细胞相关联，因此，总体而言，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，而不存在于无转移的卫星淋巴结中；它可能既依赖于原位生成（通过细胞因子产生），也依赖于从外周募集（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启示意义。
