Abstract 2654: B cells produce IL-27 in breast cancer to upregulate PD-L1 expression and promote tumor progression

B cells frequently infiltrate breast cancer (BCa) tumors, but their roles are inadequately understood. As shown by our analyses of the TCGA datasets and human BCa arrays, tumoral expression of B cell hallmark factors (e.g., CD20 and PAX5) coincides with those of the two subunits of pleiotropic cytokine IL-27, EBI3 and IL-27p28, whose expression is associated with poor prognosis in patients. In syngeneic mouse models, B cells promote BCa progression and do so by producing IL-27, but not IL-35 (IL-12/EBI3 heterodimer). Upon treatment by recombinant IL-27 or co-culturing with IL-27-producing B cells, BCa cells as well as targeted B lymphocytesactivate STAT1/STAT3 and upregulate immune checkpoint PD-L1 and chemokine receptor CXCR3, blocking of which synergistically arrest BCa cell proliferation in vitro and tumor growth in vivo, concomitant with reduction in PD-L1+B cells. Finally, B cell-specific deficiency in IL-27 receptor or PD-L1 inhibits BCa tumorigenesis, showing the dual functions of tumor-infiltrating B cells, i.e., IL-27 production for paracrinic PD-L1 upregulation. Citation Format: Hui Yan, Suryavathi Viswanadhapalli, Dariela Perez, Daniel Chupp, Maria Fernandez, Jingwei Wang, Shuai Wu, Carlos E. Rivera, Justin B. Moroney, Julia Taylor, John Im, Yiliao Luo, Junhao Liu, Sareddy Gangadhara, Tyler Curiel, Paolo Casali, Ratna Vadlamudi, Zhenming Xu. B cells produce IL-27 in breast cancer to upregulate PD-L1 expression and promote tumor progression [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2654.