Abstract A13: Siglec-7/9-sialic acid interactions inhibit T cell immune response in prostate cancer

Abstract Immunotherapy has rapidly expanded in the care of patients with cancer with the discovery of immune checkpoints like PD-1 and CTLA-4. However, current immune checkpoint inhibitors are largely ineffective for prostate cancer. Recent studies suggest an alternative immune evasion pathway through the interactions between Sialic acid-binding immunoglobulin-type lectin proteins (Siglec) and their ligands, sialylated glycoprotein. Siglec-7/9-sialic acid interactions are reported to inhibit the immune cell response in several cancer types including leukemia, melanoma, and non-small cell lung cancer. Here, we demonstrated that Siglec-7/9 ligands were expressed in both prostate cancer tumor tissues and cell lines. We promoted T cell-mediated cytotoxicity of cancer cells by disrupting the interactions between Siglec-7/9 and their ligands. We discovered that FXYD5 and CD59 are potential Siglec-7 and Siglec-9 ligands, respectively, with CRISPRi screen. We then found that FXYD5 and CD59 knockout cells had reduced Siglec-7/9 binding capacity and enhanced T cells mediated killing effects on prostate cancer cells. These results provide a rationale for novel immune checkpoints and potential approaches for targeting Siglec-7/FXYD5 and Siglec-9/CD59 immune checkpoints for prostate cancer. Citation Format: Ru M Wen, Jessica C. Stark C Stark, Fernando García-Marqués, Hongjuan Zhao, Rosie Nolley, Carolyn R Bertozzi, Sharon J Pitteri, James D. Brooks. Siglec-7/9-sialic acid interactions inhibit T cell immune response in prostate cancer [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 A13.