RESUMEN
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.
Asunto(s)
Antígenos CD5/genética , Activación de Linfocitos/inmunología , Linfocitos Infiltrantes de Tumor/inmunología , Linfocitos Infiltrantes de Tumor/patología , Melanoma Experimental/prevención & control , Linfocitos T Citotóxicos/inmunología , Linfocitos T Citotóxicos/patología , Regulación hacia Arriba/inmunología , Animales , Antígenos CD5/metabolismo , Carcinoma Pulmonar de Lewis/genética , Carcinoma Pulmonar de Lewis/patología , Carcinoma Pulmonar de Lewis/prevención & control , Muerte Celular/genética , Muerte Celular/inmunología , Línea Celular Tumoral , Citotoxicidad Inmunológica/genética , Humanos , Tolerancia Inmunológica/genética , Activación de Linfocitos/genética , Melanoma Experimental/genética , Melanoma Experimental/patología , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Receptores de Antígenos de Linfocitos T/biosíntesis , Receptores de Antígenos de Linfocitos T/genética , Linfocitos T Citotóxicos/metabolismo , Regulación hacia Arriba/genéticaRESUMEN
The destruction of tumor cells by the immune system is under the control of positive and negative receptors that tightly regulate T-cell effector functions. The T-cell receptor (TCR) inhibitory molecule CD5 critically contributes to the regulation of antitumor immune responses. Indeed, the modulation of CD5 within the tumor microenvironment corresponds to a strategy adopted by tumor-specific cytotoxic T lymphocytes (CTLs) to optimize their cytotoxic and cytokine secretion functions. In this review, we provide insights into the immunobiology of CD5 and its role in regulating antitumor CD8 T-cell responses, and suggest the possibility of targeting CD5 to improve the efficacy of current immunotherapeutic approaches against cancer.