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

Tumor immune cell infiltration plays an important role in determining treatment response and prognosis in colorectal cancer (CRC). This study aimed to investigate the association between tumor immune landscape and clinical outcomes in CRC patients receiving infusional 5-fluorouracil/leucovorin combined with either oxaliplatin (FOLFOX) or irinotecan (FOLFIRI)-based chemotherapy. Immune cell infiltration profiles were evaluated using transcriptomic data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, and the relative proportions of 22 immune cell subtypes were estimated using the CIBERSORTx algorithm. Associations between immune cell infiltration and treatment response, progression-free survival (PFS), and overall survival (OS) were systematically analyzed. A total of 511 CRC patients were included in the analysis. In patients receiving FOLFOX chemotherapy, improved drug response rates were positively associated with increased infiltration of M1 macrophages, whereas higher levels of gamma delta (γδ) T cells were correlated with poorer treatment response and reduced OS. In patients treated with FOLFIRI, elevated infiltration of M1 macrophages, M2 macrophages, activated natural killer (NK) cells, and T follicular helper (Tfh) cells was associated with unfavorable OS. Consensus clustering analysis identified three distinct immune subtypes, among which one subtype exhibited superior drug response rates and improved clinical outcomes following FOLFIRI treatment and was characterized by enrichment of adaptive immune cells, particularly memory CD4⁺ T cells and B cell-related populations. These findings demonstrate that specific immune cell subtypes and immunologically defined tumor subgroups are significantly associated with chemotherapy response and survival outcomes in CRC patients, highlighting the potential of tumor immune profiling as a predictive biomarker for chemotherapy efficacy.