Significance of Th1 and Th2 Cell Densities and Th1/Th2 Cytokine Profiles in Colorectal Cancer

Abstract

BACKGROUND: T-cell densities are associated with colorectal cancer outcome, but the significance of specific Th cell subsets is incompletely understood. We aimed to investigate the role of Th1 and Th2 cells and associated cytokine profiles.METHODS: We used multiplex IHC to identify Th1 and Th2 cells on tumor samples of more than 2,000 patients with colorectal cancer (three independent cohorts). We measured serum levels of Th1 and Th2 cytokines in mesenteric (N = 77) and peripheral (N = 603) blood samples. We evaluated the prognostic significance of Th1 and Th2 cells and their associations with circulating cytokines.RESULTS: High densities of both Th1 and Th2 cells were independently associated with better cancer-specific survival. In the largest cohort, the HR for high vs. low Th1 density was 0.62 (95% confidence interval, 0.44-0.85; PTrend = 0.004) and the HR for high vs. low Th2 density was 0.50 [95% confidence interval, 0.36-0.69; PTrend < 0.001]. Th1 cell density positively correlated with IL12 levels and negatively with IL10 levels in mesenteric serum. Th1:Th2 cell density ratio positively correlated with mesenteric serum Th1:Th2 produced cytokine ratio.CONCLUSIONS: This study supports the prognostic significance of Th1 and Th2 cells in colorectal cancer. Mesenteric serum levels of Th-related cytokines may contribute to or reflect the tumor-associated Th1/Th2 response.IMPACT: Findings highlight comparable roles for Th1 and Th2 cells in predicting favorable outcome and challenge the traditional notion of Th2 cells as tumor promoters.