title: Rescue of tumor-infiltrating lymphocytes from activation-induced cell death enhances the antitumor CTL response in CD5-deficient mice.
abstract: The CD5 coreceptor is expressed on all T cells and on the B1a B cell subset. It is associated with TCR and BCR, and modulates intracellular signals initiated by both Ag receptor complexes. Human CD5 contributes to regulation of the antitumor immune response and susceptibility of specific CTL to activation-induced cell death (AICD) triggered by the tumor. In this study, we compared the T cell response to the B16F10 melanoma engrafted into CD5-deficient and wild-type C57BL/6 mice. Compared with wild-type mice, CD5 knockout animals displayed delayed tumor growth, associated with tumor infiltration by T cell populations exhibiting a more activated phenotype and enhanced antitumor effector functions. However, control of tumor progression in CD5(-/-) mice was transient due to increased AICD of CD8(+) tumor-infiltrating T lymphocytes. Remarkably, in vivo protection of T cells from TCR-mediated apoptosis by an adenovirus engineered to produce soluble Fas resulted in a dramatic reduction in tumor growth. Our data suggest that recruitment of tumor-specific T cells in the tumor microenvironment occurs at early stages of cancer development and that tumor-mediated AICD of tumor-infiltrating T lymphocytes is most likely involved in tumor escape from the immune system.
authors.affiliation: INSERM U753, Team 1, Tumor Antigens and T Lymphocyte Reactivity, Institut de Cancérologie Gustave Roussy, 94805 Villejuif Cedex, France.
authors.forename: Mouna
authors.initials: M
authors.lastname: Tabbekh
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Franciszkiewicz
authors.forename: Houda
authors.initials: H
authors.lastname: Haouas
authors.forename: Yann
authors.initials: Y
authors.lastname: Lécluse
authors.forename: Karim
authors.initials: K
authors.lastname: Benihoud
authors.forename: Chander
authors.initials: C
authors.lastname: Raman
authors.forename: Fathia
authors.initials: F
authors.lastname: Mami-Chouaib
mesh_terms: D000818:Animals; D018956:CD5 Antigens / Q000235:genetics* / Q000378:metabolism; D018827:Carcinoma, Lewis Lung / Q000235:genetics / Q000473:pathology / Q000517:prevention & control; D016923:Cell Death / Q000235:genetics / Q000276:immunology; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D006801:Humans; D007108:Immune Tolerance / Q000235:genetics; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology* / Q000473:pathology*; D008546:Melanoma, Experimental / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011948:Receptors, Antigen, T-Cell / Q000096:biosynthesis / Q000235:genetics; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology*
chemical_list: D018956:CD5 Antigens; C526836:Cd5 protein, mouse; D011948:Receptors, Antigen, T-Cell