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

Gilberto Filaci, Daniela Fenoglio, Marco Fravega, Gianluca Ansaldo, Giacomo Borgonovo, Paolo Traverso, Barbara Villaggio, Alessandra Ferrera, Annalisa Kunkl, Marta Rizzi, Francesca Ferrera, Piercesare Balestra, Massimo Ghio, Paola Contini, Maurizio Setti, Daniel Olive, Bruno Azzarone, Giorgio Carmignani, Jean Louis Ravetti, Giancarlo TorreFrancesco Indiveri

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)4323-4334
Number of pages12
JournalJournal of Immunology
Volume179
Issue number7
Publication statusPublished - Oct 1 2007

ASJC Scopus subject areas

  • Immunology

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    Filaci, G., Fenoglio, D., Fravega, M., Ansaldo, G., Borgonovo, G., Traverso, P., Villaggio, B., Ferrera, A., Kunkl, A., Rizzi, M., Ferrera, F., Balestra, P., Ghio, M., Contini, P., Setti, M., Olive, D., Azzarone, B., Carmignani, G., Ravetti, J. L., ... Indiveri, F. (2007). CD8+CD28- T regulatory lymphocytes inhibiting T cell proliferative and cytotoxic functions infiltrate human cancers. Journal of Immunology, 179(7), 4323-4334.