Immunomodulatory effects of soluble CD5 on experimental tumor models

Modulation of antitumor immune responses by targeting immune checkpoint regulators has been proven successful in the treatment of many different tumors. Recent evidence shows that the lymphocyte receptor CD5 -a negative regulator of TCR-mediated signaling- may play a role in the anti-tumor immune response. To explore such an issue, we developed transgenic C57BL/6 mice expressing a soluble form of human CD5 (shCD5EmicroTg), putatively blocking CD5-mediated interactions ("decoy receptor" effect). Homozygous shCD5EmicroTg mice showed reduced growth rates of tumor cells of melanoma (B16-F0) and thymoma (EG7-OVA) origin. Concomitantly, increased CD4⁺ and CD8⁺ T cell numbers, as well as reduced proportion of CD4⁺CD25⁺FoxP3⁺ (T_reg) cells were observed in tumor draining lymph nodes (TdLN). TdLN cell suspensions from tumor-bearing shCD5EmicroTg mice showed increased both tumor specific and non-specific cytolitic activity. Moreover, subcutaneous peritumoral (p.t.) injection of recombinant shCD5 to wild-type (WT) mice slowed B16-F0 tumor growth, and reproduced the above mentioned TdLN cellular changes. Interestingly, lower intratumoral IL-6 levels -an inhibitor of Natural Killer (NK) cell cytotoxity- were observed in both transgenic and rshCD5-treated WT mice and the anti-tumor effect was abrogated by mAb-induced NK cell depletion. Taken together, the results further illustrate the putative regulatory role of CD5-mediated interactions in anti-tumor immune responses, which would be at least in part fostered by NK cells.