B cells inhibit the antitumor immunity against an established murine fibrosarcoma

Maglioco,Andrea; Machuca,Damián  G.; Badano,María  Noel; Nannini,Paula; Camerano,Gabriela  V.; Costa,Héctor; Meiss,Roberto; Ruggiero,Raúl  A.; Giordano,Mirta; Dran,Graciela  I.

doi:10.3892/ol.2017.5810

B cells inhibit the antitumor immunity against an established murine fibrosarcoma

Authors:
- Andrea Maglioco
- Damián G. Machuca
- María Noel Badano
- Paula Nannini
- Gabriela V. Camerano
- Héctor Costa
- Roberto Meiss
- Raúl A. Ruggiero
- Mirta Giordano
- Graciela I. Dran
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Affiliations: Laboratory of Experimental Oncology, Institute of Experimental Medicine (IMEX), The National Scientific and Technical Research Council (CONICET), National Academy of Medicine, Buenos Aires C1425AUM, Argentina, Laboratory of Experimental Immunology, IMEX, CONICET, National Academy of Medicine, Buenos Aires C1425AUM, Argentina, Laboratory of Cancer Immunology, IMEX, CONICET, National Academy of Medicine, Buenos Aires C1425AUM, Argentina, IMEX, CONICET, National Academy of Medicine, Buenos Aires C1425AUM, Argentina , Department of Pathology, Institute of Oncology Studies, National Academy of Medicine, Buenos Aires C1425AUM, Argentina
Published online on: March 6, 2017 https://doi.org/10.3892/ol.2017.5810
Pages: 3225-3232

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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.

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