Abstract A46: Neoantigen-driven B and T follicular helper cell collaboration promotes anti-tumor CD8 T cell responses


 CD4 T follicular helper (TFH) cells and B cells are essential components of germinal center (GC) response, but the importance and mechanisms of TFH-B cell collaborations in malignancy are unclear. The presence of TFH, B cells and GC has been associated with favorable clinical outcomes and improved therapeutic responses to checkpoint blockade immunotherapy in numerous types of solid tumors. We found enrichment of TFH cell transcriptional signature correlates with prolonged survival in lung adenocarcinoma (LUAD) individuals. To further investigate if and how TFH-B cell interactions elicit protective anti-tumor responses, we developed the KP-HELLO murine lung adenocarcinoma model, in which tumor cells expressed B-cell- and T-cell-recognized neoantigens (HEL, LCMV GP33-43/FLAG/GP61-80, and codon-Optimized mScarlet). Collaborations between tumor-specific TFH and B cells, as well as interleukin (IL)-21 primarily produced by TFH cells, are necessary for tumor control and effector CD8 T cell function. Development of TFH cells and IL-21 production requires B cells and B cell-recognized neoantigens. We demonstrated that tumor neoantigens can educate the differentiation of tumor-specific CD4 T cells and regulate their fate by facilitating their interactions with tumor-specific B cells, which in turn promote anti-tumor immunity by enhancing CD8 T cell effector functions.
 Citation Format: Can Cui, Joseph Craft, Nikhil S. Joshi. Neoantigen-driven B and T follicular helper cell collaboration promotes anti-tumor CD8 T cell responses [abstract]. In: Proceedings of the AACR Special Conference: Tumor Immunology and Immunotherapy; 2022 Oct 21-24; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2022;10(12 Suppl):Abstract nr A46.