The infiltration pattern of microenvironmental cells and different immune escape mechanisms in colorectal cancer

Background: The tumour microenvironment (TME) plays a crucial role in tumour progression and metastasis. However, the infiltration pattern of TME cells in CRC samples and the immune escape mechanism underneath have not been studied sufficiently. Methods: Transcriptomic data from public datasets were retrieved online. In total, 1802 samples from the microarray dataset and 619 samples from the TCGA dataset were enrolled. The ssGSEA algorithm and unsupervised clustering were used for TME cells infiltration speculation and infiltration pattern recognition. Findings: CRC samples can be classified into three distinct TME cell subtypes. Subtype 1, the immune-active subtype, was characterised by high infiltration of activated adaptive immune cells. Subtype 2, the immune-desert subtype, featured high tumour purity and low infiltration of immune and stromal cells. And subtype 3, stroma-rich subtype, had high infiltration of stromal cells. The stroma-rich subtype conferred a significantly worse prognosis. Three subtypes had different immune escape mechanisms. The immune-active subtype has the highest immune checkpoint expression level. In comparison, the immune-desert subtype had the lowest immunogenicity and the defective antigen presentation. And the stroma-rich subtype lacked activated immune cells. Interpretation: Distinct TME cell subtypes and immune escape mechanisms may provide inspiration and direction for further researches on CRC immunotherapy. Funding Information: This work was supported by the National Natural Science Foundation of China (No. 82002517, 82072678), the Shanghai Sailing Program (20YF1407100), and Shanghai Science and Technology Committee Project (18140903200). Declaration of Interests: The authors report no conflict of interest.