Oncotarget

Research Papers:

Immunomodulatory effects of soluble CD5 on experimental tumor models

Inês T. Simões, Fernando Aranda, Esther Carreras, Maria Velasco-de Andrés, Sergi Casadó-Llombart, Vanesa G. Martinez and Francisco Lozano _

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Oncotarget. 2017; 8:108156-108169. https://doi.org/10.18632/oncotarget.22564

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Abstract

Inês T. Simões1, Fernando Aranda1, Esther Carreras1, Maria Velasco-de Andrés1, Sergi Casadó-Llombart1, Vanesa G. Martinez1,* and Francisco Lozano1,2,3,*

1Immunoreceptors of the Innate and Adaptive System, Institut d’Investigacions Biomèdiques August Pi i Sunyer, 08036, Barcelona, Spain

2Servei d’Immunologia, Centre de Diagnòstic Biomèdic, Hospital Clínic de Barcelona, 08036, Barcelona, Spain

3Departament de Biomedicina, Facultat de Medicina, Universitat de Barcelona, 08036, Barcelona, Spain

*These authors share senior authorship

Correspondence to:

Francisco Lozano, email: FLOZANO@clinic.ub.es

Keywords: CD5; immunotherapy; immune-checkpoint; T regulatory cells; NK cells

Received: May 24, 2017    Accepted: September 13, 2017    Published: November 20, 2017

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.


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