B cells inhibit the antitumor immunity against an established murine fibrosarcoma

DAMIAN MACHUCA; CAMERANO G; RAÚL A. RUGGIERO; BADANO N; ANDREA MAGLIOCO; ANDREA MAGLIOCO; COSTA H; NANNINI P; NANNINI P; GIORDANO M; MEISS R; MEISS R; DAMIAN MACHUCA; GRACIELA DRAN; GRACIELA DRAN; CAMERANO G; BADANO N; RAÚL A. RUGGIERO; COSTA H; GIORDANO M

Oncology Letters

Spandidos Publications

Año: 2017 p. 3225 - 3232

1792-1074

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.