Several immune checkpoint blockers have been approved for treatment of certain cancers, which benefits a lot of patients with malignancies. However, the overall response rate to the current checkpoint blockers did not exceed 30% in many cases, stressing the importance of developing new immunotherapies. Siglec-15 is reported to be a critical immune suppressor functioning in parellel with PD1/PD-L1 pathway by Lieping Chen's lab in 2019. In order to verify the effect Siglec-15 in immune response against tumor growth, we generated Siglec-15 KO mice with CRISPR/Cas9 mediated genome editing and tested tumor establishment on this mice with syngeneic cell lines with or without human SIGLEC-15 overexpression. Our results showed that Siglec-15 KO inhibits tumor growth and enhances immune response in the tumor infiltrating leukocytes, supporting the role of Siglec-15 as a promising target for development of new immune checkpoint blocker.

Citation Format: Peixue Li, Guofang Yan, Fuyang Wang, Xuzhen Tang, Qing Lin. Siglec-15 knockout inhibits tumor growth in mouse model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1634.