CD8+CD28- T regulatory lymphocytes inhibiting T cell proliferative and cytotoxic functions infiltrate human cancers

被引:184
作者
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
机构
[1] Univ Genoa, Dept Internal Med, I-16132 Genoa, Italy
[2] Univ Genoa, Ctr Excellence Biomed Res, I-16132 Genoa, Italy
[3] Univ Genoa, Dept Surg & Morphol Disciplines & Integrated Meth, Genoa, Italy
[4] Univ Genoa, Dept Urol, Genoa, Italy
[5] Osped San Martino Genova, Genoa, Italy
[6] Univ Aix Marseille 2, Inst J Paoli I Calmettes, INSERM, UMR 599,Lab Immunol Tumeurs, Marseille, France
[7] Hop Paul Brousse, INSERM, Unite 542, Villejuif, France
关键词
D O I
10.4049/jimmunol.179.7.4323
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:4323 / 4334
页数:12
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