Tumour immune cell infiltration and response to FOLFOX or FOLFIRI chemotherapy in colorectal cancer

Abstract Background: The immune cell infiltration of tumors has been demonstrated to have a significant part in the response to different cancer treatments. We sought to gain greater understanding of the connections between the immune landscape of colorectal cancer (CRC) tumors and the clinical outcomes of infusional 5-fluorouracil/leucovorin with either oxaliplatin (FOLFOX) or irinotecan (FOLFIRI)-based chemotherapy. Methods: The immune cell infiltration of CRC tumors was evaluated using data from the TCGA and GEO databases with the CIBERSORTx algorithm. The relative proportion of 22 immune cell subtypes was measured, and their associations with response, progression-free survival (PFS), and overall survival (OS) were investigated. Consensus clustering analysis was utilized for the identification of the immune cell patterns. Results: We analyzed data from 387 CRC patients and found that drug response rates were negatively correlated with M1 macrophages in the context of FOLFOX chemotherapy. Poor PFS was linked to resting dendritic cells and eosinophils in this regimen. An inverse relationship between drug response rate and M0 macrophages was observed within the FOLFIRI chemotherapy regimen. Activated natural killer cells were connected to poor PFS and OS. Using consensus clustering analysis, we identified three immunological clusters, with a cluster associated with better medication response rates and improved patient outcomes following FOLFOX treatment. This cluster was characterized by higher proportions of M0 macrophages, quiescent memory CD4+ T cells, and quiescent B cells. Conclusion: Our findings emphasize the significant impact of the CRC tumor-immune milieu on the response to FOLFOX or FOLFIRI chemotherapy. Further investigation of its regulatory mechanisms may contribute to advancements in therapeutic interventions.