Abstract B045: Immunosuppressive plasmocytes impede T-cell-dependent immunogenic chemotherapy

Abstract Cancer-associated genetic alterations induce expression of tumor antigens that can activate CD8+ cytotoxic T cells (CTLs), but the microenvironment of established tumors promotes immune tolerance through poorly understood mechanisms. Recently developed therapeutics that overcome tolerogenic mechanisms activate tumor-directed CTLs and are effective in some human cancers. Immune mechanisms also affect treatment outcome and certain chemotherapeutic drugs stimulate cancer-specific immune responses by inducing immunogenic cell death and other effector mechanisms. Because castrate-resistant prostate cancer is refractory to most therapies, we examined B cell involvement in the acquisition of chemotherapy resistance. Here we focus on oxaliplatin, an immunogenic chemotherapeutic that is effective in aggressive prostate cancer. Mouse B cells modulate the response to low-dose oxaliplatin, which promotes tumor-directed CTL activation by inducing immunogenic cell death. Three different mouse prostate cancer models were refractory to oxaliplatin unless genetically or pharmacologically depleted of B cells. The crucial immunosuppressive B cells are plasmocytes that express IgA, interleukin (IL)-10 and programmed death ligand 1 (PD-L1), the appearance of which depends on TGFβ receptor signaling. Elimination of these cells, which also infiltrate human-therapy-resistant prostate cancer, allows CTL-dependent eradication of oxaliplatin-treated tumors. Citation Format: Shabnam Shalapour, Michael Karin. Immunosuppressive plasmocytes impede T-cell-dependent immunogenic chemotherapy. [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 B045.