title: CD8+ CD28- T regulatory lymphocytes inhibiting T cell proliferative and cytotoxic functions infiltrate human cancers.
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.
authors: Centre of Excellence for Biomedical Research, University of Genoa, Genoa, Italy.
authors: Gilberto
authors: G
authors: Filaci
authors: Daniela
authors: D
authors: Fenoglio
authors: Marco
authors: M
authors: Fravega
authors: Gianluca
authors: G
authors: Ansaldo
authors: Giacomo
authors: G
authors: Borgonovo
authors: Paolo
authors: P
authors: Traverso
authors: Barbara
authors: B
authors: Villaggio
authors: Alessandra
authors: A
authors: Ferrera
authors: Annalisa
authors: A
authors: Kunkl
authors: Marta
authors: M
authors: Rizzi
authors: Francesca
authors: F
authors: Ferrera
authors: Piercesare
authors: P
authors: Balestra
authors: Massimo
authors: M
authors: Ghio
authors: Paola
authors: P
authors: Contini
authors: Maurizio
authors: M
authors: Setti
authors: Daniel
authors: D
authors: Olive
authors: Bruno
authors: B
authors: Azzarone
authors: Giorgio
authors: G
authors: Carmignani
authors: Jean Louis
authors: JL
authors: Ravetti
authors: Giancarlo
authors: G
authors: Torre
authors: Francesco
authors: F
authors: Indiveri
mesh_terms: D018106:CD28 Antigens / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D002454:Cell Differentiation; D049109:Cell Proliferation; D003602:Cytotoxicity, Immunologic; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis; D008207:Lymphatic Metastasis / Q000276:immunology / Q000473:pathology; D009367:Neoplasm Staging; D009369:Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D010641:Phenotype; D054390:Receptors, CCR2; D054398:Receptors, CCR4; D019707:Receptors, Chemokine / Q000378:metabolism; D015996:Survival Rate
chemical_list: C515334:CCR2 protein, human; C515354:CCR4 protein, human; D018106:CD28 Antigens; D054390:Receptors, CCR2; D054398:Receptors, CCR4; D019707:Receptors, Chemokine; D016753:Interleukin-10; D016178:Granulocyte-Macrophage Colony-Stimulating Factor