Density of T cell subsets in colorectal cancer in relation to disease-specific survival.

Abstract

Background: Prior studies have demonstrated that the overall density of T cells in colorectal tumors is favorably associated with colorectal cancer (CRC) survival; however, few studies have considered the potentially distinct roles of heterogeneous T cell subsets in different tissue regions in relation to CRC outcomes.

Methods: Including 1,113 CRC tumors from three observational studies, we conducted in-situ T cell profiling using a customized 9-plex [CD3, CD4, CD8, CD45RA, CD45RO, FOXP3, KRT (keratin), MKI67 (Ki-67), and DAPI] multispectral immunofluorescence assay. Multivariable-adjusted Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations of T cell subset densities in both epithelial and stromal tissue areas in CRC with disease-specific survival.

Results: Higher CD3+CD4+ and CD3+CD8+ naive, memory, and regulatory T cell densities were significantly associated with better CRC-specific survival in both epithelial and stromal tissue areas (HRs highest quantile versus lowest quantile ranging 0.41-0.68). These associations persisted in models further adjusted for stage at diagnosis and were largely consistent when stratified by microsatellite instability (MSI) status. However, the further stratification into CD4+ or CD8+ T cell subsets beyond CD3+ subsets did not significantly improve how well our model explains CRC prognosis.

Conclusions: The density of T cells in CRC tissue, both overall and for several T cell subset populations, is significantly associated with CRC-specific survival independent of MSI status and stage at diagnosis.

Impact: Higher levels of T cell densities in different locations with different functions are associated with better CRC-specific survival.