CD8+ CD28- T regulatory lymphocytes inhibiting T cell proliferative and cytotoxic functions infiltrate human cancers.
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.
Filaci
Gilberto
G
Centre of Excellence for Biomedical Research, University of Genoa, Genoa, Italy.
Fenoglio
Daniela
D
Fravega
Marco
M
Ansaldo
Gianluca
G
Borgonovo
Giacomo
G
Traverso
Paolo
P
Villaggio
Barbara
B
Ferrera
Alessandra
A
Kunkl
Annalisa
A
Rizzi
Marta
M
Ferrera
Francesca
F
Balestra
Piercesare
P
Ghio
Massimo
M
Contini
Paola
P
Setti
Maurizio
M
Olive
Daniel
D
Azzarone
Bruno
B
Carmignani
Giorgio
G
Ravetti
Jean Louis
JL
Torre
Giancarlo
G
Indiveri
Francesco
F
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
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