IDDF2021-ABS-0183\u2005SLC25A22 drives immune suppression in kras-mutant colorectal cancer

Abstract

Background Direct targeting of KRAS is challenging and represents an unmet need. We identified SLC25A22, a mitochondrial glutamate transporter, as a potential therapeutic target in KRAS mutant colorectal cancer (CRC). In this study, we reveal that SLC25A22 underlies mutant KRAS-induced immune suppression in CRC. Methods Immune cell infiltration was determined by flow cytometry. The immunosuppressive effect and migration of MDSC were estimated by T cell suppression assay and transwell assay, respectively. Results Tumors from ApcMin/+KrasG12DVillin-Cre mice demonstrated marked infiltration in immunosuppressive myeloid-derived suppressor cells (MDSC) (P (IDDF2021-ABS-0183 Figure 5. SLC25A22 recruits MDSC migration via CXCL1/CXCR2 axis, IDDF2021-ABS-0183 Figure 6. SLC25A22 recruits MDSC migration via CXCL1/CXCR2 axis) Conclusions Our work suggests a SLC25A22-chemokine axis that promotes an immune suppressive microenvironment in KRAS-mutant CRC and implies that SLC25A22 constitutes a novel target for immunotherapies.