B lymphocytes play a role in inhibiting the immune response against certain tumors, but the underlying mechanisms are poorly understood. EMT-6 mammary tumors grow well in wild type (WT) mice but show reduced growth in B-cell deficient μ-/- BALB/c mice (BCDM). WT mice demonstrate B cell infiltration into the tumor bed and a reduced cytolytic T cell response relative to BCDM. Expression of LAP/TGF-β1, CD80, CD86 and PDL-1 is increased in tumor infiltrating B cells (TIL-B) relative to splenic B cells. LAP/TGF-β1 expression progressively increased from 5.4±1.7% on d8 to 43.1±6.1% of TIL-B by d21 post tumor implantation. Co-culture of EMT-6 tumor cells with naïve B cells generated B cells (EMT6-B) with a similar immunophenotype to TIL-B. Purified TIL-B or in vitro generated EMT6-B markedly suppressed CD4+CD25- T cell proliferation, and Th1 cytokine secretion compared to naïve splenic B cells. Acquired B regulatory function required direct tumor cell: B cell contact, and was partially reversed by antibody to TGF-β1 or PDL-1, leading to tumor rejection in vivo. B cell acquisition of a suppressive phenotype following tumor infiltration may result in profound inhibition of T cell anti-tumor response. Similar B cell mediated immunosuppression may be operative in human solid tumors.
Citation Format: Yu Zhang, Richard Morgan, Chuan Chen, Yancheng Cai, Seung-Uon Shin, Hyun-Mi Cho, Ahmed Al Bayati, Augustin Pimental, Joseph D. Rosenblatt. Tumor-educated B cells acquire LAP/TGF-β1 and PD-L1 expression and suppress antitumor immune response. [abstract]. In: Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr A120.
- ©2016 American Association for Cancer Research.