Alteration in the Immune Microenvironment Based on APC Status in MSS/pMMR Colon Cancer Data Retrieved from TCGA

Abstract

BackgroundImmunotherapy is currently the most advanced anti-tumor treatment approach. The efficacy of anti-tumor immunotherapy is closely related to the tumor immune microenvironment, including immune cells, infiltration of immune factors, and expression of immune checkpoints. At present, the biomarkers for predicting the efficacy of colon cancer immunotherapy do not cover all colon cancer patients suitable for immunotherapy. In this study, TCGA database was used to identify tumor genotypes suitable for anti-tumor immunotherapy. MethodsWe downloaded 390 samples with RNA-sequencing data and somatic mutation status data from TCGA. We applied the ESTIMATE, Package limma, the CIBERSORT and some other algorithms to analyze the cellular immune microenvironment. And validated with immunohistochemistry in tumor tissues of colon cancer patients. ResultsWe found that some of the MSS/pMMR populations, that were initially considered unsuitable for immunotherapy, might actually be suitable. In APC-wt/MSS colon cancer, the expression of PD-1, PD-L1, CTLA4 and CYT（GZMA and PRF1）were increased. Based on calculations done by ESTIMATE and CIBERSORT algorithms, the ImmunoScore and the proportion of CT8+ T cell infiltration is increased in these patients. Enrichment analysis was done to screen signaling pathways involved in immune response, extracellular matrix, and cell adhesion. Tumors from 42 colon cancer patients, including 22 APC-mt/MSS and 20 APC-wt/MSS, were immunohistochemically evaluated for expression of CD8 and PD-L1. And APC-wt/MSS tumors showed significantly higher expression of CD8 and PD-L1 than APC-mt/MSS tumor. ConclusionsBased on the results, we found that some colon cancers of APC-wt/MSS are classified by Tumor Immune Microenvironment types (TIMTs) TMIT I. So that we speculate that APC-wt/MSS colon cancer patients could benefit from anti-tumor immunotherapy.

Alteration in the Immune Microenvironment Based on APC Status in MSS/pMMR Colon Cancer

“…In addition, we selected 42 patients' colon cancer tissues, including 22 cases of APC-mt/MSS and 20 APC-wt/MSS, to performed immunohistochemistry to further confirm that APC-wt/MSS contained more TIMT type I tumors, and had a higher DCR for ICIs. A preprint has previously been published [ 22 ]. APC is a protein that assists in inactivating β -catenin in the Wnt pathway [ 23 ].…”