Age, sex, and specific gene mutations affect the effects of immune checkpoint inhibitors in colorectal cancer.

Abstract

e16103 Background: The effect of age and sex on the prognosis of colorectal cancer (CRC) patients treated with immune checkpoint inhibitors (ICIs) has been controversial, and the effect of specific gene mutations on the prognosis of patients treated with ICIs remains to be explored. Based on detailed clinical and genetic data, this study analyzed the influence of the above factors on the overall survival (OS) of CRC patients after ICI treatment and explored the influencing mechanism of various prognostic factors. Methods: We performed survival prognostic correlation analysis and bioinformatics analysis on the clinical CRC cohort receiving ICIs published by Samstein et al. and the clinical and genetic data from The Cancer Genome Atlas (TCGA)-CRC dataset, including immunogenicity and immunosignature analysis, DNA damage response and repair (DDR) pathway analysis, and gene set enrichment analysis (GSEA). Results: Both clinical characteristics and specific gene mutations may be prognostic factors for ICI treatment in CRC patients. Mutation count > 11 (tumor mutation burden (TMB)-high), age > 65, male, RNF43, CREBBP, NOTCH3, PTCH1, CIC, DNT1, and SPEN mutant (MT) were associated with longer OS, while APC-mMT and TP53-MT were significantly correlated with shorter OS. The reason why protective prognostic markers provide better survival benefits to CRC patients may be related to factors such as higher immunogenicity, highly infiltrated immunoactive cells and active immunoactive pathways. Conclusions: Our study is the first to elucidate comprehensive prognostic factors for the treatment of ICIs in CRC patients, from clinical characteristics such as age and sex to specific gene mutations, providing new ideas for immunotherapy in CRC.