Assessment of compartment-specific CD103-positive cells for prognosis prediction of colorectal cancer.

BACKGROUND: CD103(+) tissue-resident memory T cells was detected in various solid malignancies, like colorectal cancer (CRC), and associated with improved survival. However, clinical significance of CD103(+) cells in specific intratumor compartment remains unclear. METHODS: The abundance and distribution of CD103(+) cells were assessed using immunohistochemistry and quantified separately for 3 compartments, including intraepithelial compartments at center of tumor (CT-IEL), stromal compartments at center of tumor (CT-ST) and invasive margin (IM) in a cohort of 224 CRC patients under radical surgery and correlated with outcome. Findings in each compartment were then validated in an external validation cohort comprising 294 CRC patients. RESULTS: Elevated density of CD103(+) cells infiltration in the CT-IEL, CT-ST or IM compartment was correlated with favorable survival in both the initial discovery cohort and subsequent validation cohort. Notably, abundant CD103(+) cells located in the CT-IEL compartment was remained an independent prognostic indicator for CRC patients by multivariant analysis. Characterization study showed that intraepithelial CD103(+) cells were predominantly single positive CD8 T cells. Conversely, CD103(+) cells exhibited a heterogeneous population comprising CD103(+)CD8(+) cells, CD103(+)CD4(+) cells, and nonconventional CD103(+)CD4(+)CD8(+) cells in the CT-ST and IM compartments. Finally, a CD103 score was generated comprising abundance of CD103(+) cells in the 3 compartments. This score had the highest relative contribution to the risk of all clinical parameters for prognosis in both cohorts. CONCLUSION: This study supported a phenotypic heterogeneity of CD103(+) cells in CRC, and provided a reliable estimate of the risk of death and recurrence in CRC patients based on combined analysis of CD103(+) cells within 3 intratumor compartments.