KALRNmutations promote antitumor immunity and immunotherapy response in cancer

• DOI: 10.1136/jitc-2019-000293
• Publication Date: 2020-10-09T21:45:37Z
• Authors: Mengyuan Li; Yuxiang Ma; You Zhong; Qian Liu; Canping Chen; Lei Qiang; Xiaosheng Wang
• Keywords: Immune checkpoint; Cancer Immunotherapy; Microsatellite Instability

Background kalirin RhoGEF kinase ( KALRN ) is mutated in a wide range of cancers. Nevertheless, the association between mutations and pathogenesis cancer remains unexplored. Identification biomarkers for immunotherapy response crucial because immunotherapies only show beneficial effects subset patients with cancer. Methods We explored correlation antitumor immunity 10 cohorts from The Cancer Genome Atlas program by bioinformatics approach. Moreover, we verified findings analysis vitro vivo experiments. five receiving immune checkpoint blockade therapy. Results Antitumor signatures were more enriched -mutated than -wildtype displayed significant correlations increased tumor mutation burden microsatellite instability or DNA damage repair deficiency genomic properties, which may explain high Also, programmed cell death 1 ligand (PD-L1) expression was markedly upregulated versus PD-L1 cancers favor to therapy this subtype, as evidenced antiprogrammed protein (PD-1)/PD-L1/cytotoxic T-lymphocyte-associated 4 (CTLA-4) immunotherapy. Furthermore, associated fact that compromised function targeting Rho GTPases regulation pathways. In experiments validated inhibitors. Conclusions useful biomarker predicting