Immunomodulatory effects of soluble CD5 on experimental tumor models.

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Immunomodulatory effects of soluble CD5 on experimental tumor models.

Oncotarget. 2017 Dec 08;8(64):108156-108169

Authors: Simões IT, Aranda F, Carreras E, Andrés MV, Casadó-Llombart S, Martinez VG, Lozano F

Abstract
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 (shCD5EμTg), putatively blocking CD5-mediated interactions ("decoy receptor" effect). Homozygous shCD5EμTg 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+ (Treg) cells were observed in tumor draining lymph nodes (TdLN). TdLN cell suspensions from tumor-bearing shCD5EμTg 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.

PMID: 29296231 [PubMed]

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