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B cells promote tumor progression in a mouse model of HPV‐mediated cervical cancer
Author(s) -
Tang Alexandre,
Dadaglio Gilles,
Oberkampf Marine,
Di Carlo Selene,
Peduto Lucie,
Laubreton Daphné,
Desrues Belinda,
Sun ChengMing,
Montagutelli Xavier,
Leclerc Claude
Publication year - 2016
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.30169
Subject(s) - tumor microenvironment , cancer research , biology , immunity , immune system , cd86 , tumor progression , immunology , mhc class i , cancer , t cell , major histocompatibility complex , genetics
Enhancing anti‐tumor immunity and preventing tumor escape are efficient strategies to increase the efficacy of therapeutic cancer vaccines. However, the treatment of advanced tumors remains difficult, mainly due to the immunosuppressive tumor microenvironment. Regulatory T cells and myeloid‐derived suppressor cells have been extensively studied, and their role in suppressing tumor immunity is now well established. In contrast, the role of B lymphocytes in tumor immunity remains unclear because B cells can promote tumor immunity or display regulatory functions to control excessive inflammation, mainly through IL‐10 secretion. Here, in a mouse model of HPV‐related cancer, we demonstrate that B cells accumulated in the draining lymph node of tumor‐bearing mice, due to a prolonged survival, and showed a decreased expression of MHC class II and CD86 molecules and an increased expression of Ly6A/E, PD‐L1 and CD39, suggesting potential immunoregulatory properties. However, B cells from tumor‐bearing mice did not show an increased ability to secrete IL‐10 and a deficiency in IL‐10 production did not impair tumor growth. In contrast, in B cell‐deficient μMT mice, tumor rejection occurred due to a strong T cell‐dependent anti‐tumor response. Genetic analysis based on single nucleotide polymorphisms identified genetic variants associated with tumor rejection in μMT mice, which could potentially affect reactive oxygen species production and NK cell activity. Our results demonstrate that B cells play a detrimental role in anti‐tumor immunity and suggest that targeting B cells could enhance the anti‐tumor response and improve the efficacy of therapeutic cancer vaccines.