A high density of PD-L1-expressing immune cells is significantly correlated with favorable disease free survival in nonmetastatic colorectal cancer.

ABSTRACT: The impact of immune cells (ICs) expressing various markers remains poorly understood in nonmetastatic colorectal cancer patients who have undergone colectomy. Here, we aimed to clarify the correlation between IC density and clinical parameters and survival.Programmed death protein-1 (PD-1), programmed cell death protein ligand-1 (PD-L1), clusters of differentiation (CD)-3, CD-8, and CD45RO immunostaining was performed for 421 patients using tissue microarray and automatic counting. Tumor stroma area immune density was assessed in comparison to clinical histological factors and surgical outcomes.High-density CD-8 expression was significantly associated with current smoking habits or a smoking history (P = .006). High-density of PD-1 expression was correlated with Lynch syndrome patients (P < .001) and with patients who did not consume alcohol (P = .034). A significant decrease in CR45RO expression density was associated with aging (P = .002 and r = -0.014), and high-density CD-3, CD-8, and PD-1 expression was significantly associated with right colon tumor location (P < .001). High CD-3 and PD-L1 expression was significantly associated with early tumor T-staging (P = .018 and P = .002). High-density PD-1 expression was significantly correlated with mucinous type adenocarcinoma (P = .027) and poor differentiation (P < .001). For treatment outcomes, multivariate analysis confirmed that patients exhibiting high-density PD-L1 expression possessed significantly longer disease free survival (adjusted hazard ratio: 0.752, 95% confidence interval [CI]: 0.61-0.92, P = .006) and overall survival (adjusted hazard ratio: 0.872, 95% CI: 0.75-1.91, P = .064)Significantly varied density in IC subsets was related to distinct demographic or clinic-histological factors. The presence of high-density PD-L1-expressing ICs is an independent favorable prognostic factor for disease free survival and overall survival among stage I to III colorectal cancer patients.