Background While the administration of immunotherapy can facilitate the development of durable anti-tumor immunity in certain colorectal cancer (CRC) patients.This study was therefore designed to conduct a robust analysis of the CRC immune microenvironment to identify specific genes and pathways that can be targeted in an effort to achieve more effective immunotherapy outcomes. Methods Using five Independent data sets, we analyzed expression profiles associated with 29 different immune signatures, and we used these profiles to guide the hierarchical clustering of CRC samples based on their immune microenvironmental composition. Results We were able to cluster our CRC samples based on whether they had exhibited high, medium, or low levels of infiltration by immune cell types associated with tumor clearance (Immunity_H, Immunity_M, and Immunity_L, respectively). Samples in the Immunity_H subset exhibited a “hot” immune microenvironment, with higher stromal scores, higher immune scores, and lower tumor purity. The microsatellite instability (MSI) group included the majority of the Immunity_H samples, whereas most Immunity_M and Immunity_L samples were incorporated into the microsatellite stability (MSS) .The vast majority of patients with KRAS mutations were in the Immunity_L and MSS groups, whereas the majority of patients exhibiting BRAF V600E mutations were found in the Immunity_H and MSI-H samples. TMB high samples included a majority of the Immunity_H samples and a small subset of the Immunity_M samples. Conclusions Our results identify three reproducibly validated immune subtypes of CRC tumor samples, potentially offering valuable insights that may guide the immunotherapeutic treatment of these patients.
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