TIME (Tumor Immunity in the MicroEnvironment) classification based on tumor CD274 (PD-L1) expression status and tumor-infiltrating lymphocytes in colorectal carcinomas.

摘要: Inhibitors targeting the PDCD1 (programmed cell death 1, PD-1) immune checkpoint pathway have revolutionized cancer treatment strategies. The TIME (Tumor Immunity in MicroEnvironment) classification based on tumor CD274 (PDCD1 ligand PD-L1) expression and tumor-infiltrating lymphocytes (TIL) has been proposed to predict response immunotherapy. It remains be determined clinical, pathological, molecular features of subtypes colorectal cancer. Using 812 colon rectal carcinoma cases from Nurses' Health Study Professionals Follow-up Study, we examined association characteristics survival outcomes with four (TIME CD274low/TILabsent; 2, CD274high/TILpresent; 3, CD274low/TILpresent; 4, CD274high/TILabsent). In analyses, Cox proportional hazards models were adjusted for potential confounders, including microsatellite instability (MSI) status, CpG island methylator phenotype (CIMP) LINE-1 methylation level, KRAS, BRAF, PIK3CA mutation status. 3 4 had 218 (27%), 117 (14%), 103 (13%), 374 (46%) cases, respectively. Compared TIL-absent 1 4), TIL-present 2 3) associated high-level MSI, high-degree CIMP, BRAF mutation, higher amounts neoantigens (p < 0.001). not significantly cancer-specific or overall survival. conclusion, are high levels MSI neoantigen load, supporting better responsiveness Further studies examining alterations additional factors microenvironment may inform development immunoprevention immunotherapy