B cells inhibit the antitumor immunity against an established murine fibrosarcoma.

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B cells inhibit the antitumor immunity against an established murine fibrosarcoma.

Oncol Lett. 2017 May;13(5):3225-3232

Authors: Maglioco A, Machuca DG, Badano MN, Nannini P, Camerano GV, Costa H, Meiss R, Ruggiero RA, Giordano M, Dran GI

Abstract
Despite the classic role of B cells in favoring the immune response, an inhibitory action of B lymphocytes in tumor immunity has emerged in certain studies. In methylcolanthrene-induced murine fibrosarcoma (MCC), the loss of immunogenicity and the establishment of tolerance are paralleled by systemic immune suppression and the appearance of B(+)IL-10(+) cells in tumor-draining lymph nodes. The present study aimed to assess the role of the B(+)IL-10(+) cell population in the immune evasion and tolerance induced by MCC through the depletion of B cells in mice at various times of tumor progression: Prior to or subsequent to tumor implantation. Tumor growth and immunological parameters were evaluated. B cell depletion prior to tumor inoculum enhanced tumor growth, initiating the onset of the tumor-induced systemic immune response; however, an increase in the T regulatory cells (Tregs) at the tumor-draining lymph node could account for tumor exacerbation. B cell depletion once the tumor was established resulted in decreased tumor growth and a delayed onset of tolerance. Additionally, B cell absence exacerbated T cell dependent-tumor rejection, reduced Tregs and increased cytotoxic CD8(+) T cells. In vitro analysis showed a direct effect of B cells upon T cell proliferation. In conclusion, B cell depletion exerts opposite effects when performed prior to or subsequent to tumor implantation. In this initially immunogenic tumor, B cell absence would delay the establishment of immunological tolerance probably by unmasking a pre-existing antitumor response. The present findings elucidate the convenience of modulating B cells in the development of future and more effective immunotherapies against cancer.

PMID: 28521429 [PubMed - in process]

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