Tumor-associated CAIC5 suppresses NKT cell proliferation and cytokine production

Abstract

Abstract In the previous study, we identified cancer-associated immune checkpoint 5 (CAIC5) as a new co-inhibitory molecule belonging to B7-related family. Typically, CAIC5 is expressed in tissue macrophages including Kupffer cells and peritoneal macrophages. We also found out human CAIC5 fusion protein greatly suppressed the proliferation and cytokine production in T cells and NKT cells in a respective stimulation assay. Since CAIC5 expression was identified in tumor microenvironment, we examined the impact of tumor cell-associated CAIC5 on NKT cell function. CAIC5-expressing cancer cells that are pulsed with alpha-galactosylceramide (a-Gal) greatly suppressed NKT cell IFN-g production and proliferation. CAIC5 KO mice that were systemically injected with a-Gal enhanced IFN-g production in NKT cells. Furthermore, WT mice that were injected with CAIC5-expressing tumor cells showed a poor survival compared to those with mock-expressing cells. We also found out human NKT cells were similarly suppressed in IFN-g production in the coculture with CAIC5-expressing cancer cell line. Therefore, tumor CAIC5 can be an important part of mechanisms for cancer immune escape.