PD-L1+ dendritic cells in the tumor microenvironment correlate with good prognosis and CD8+ T cell infiltration in colon cancer

Abstract

Background: The prognostic value of tumor-associated dendritic cells (DC) in colon cancer remains poorly understood. This may be in part due to the interchangeable expression of immunostimulatory and immunoinhibitory molecules on DC. Here we investigated the prognostic impact of CD11c⁺ DC co-expressing the immunoinhibitory molecule PD-L1 and their spatial relationship with CD8⁺ T-cells in patients treated for stage III colon cancer.

Methods: Tissue microarrays containing representative cores of central tumor, leading edge, and adjacent normal tissue from 221 patients with stage III colon cancer were immunostained for CD8, CD11c, PD-L1, and cytokeratin using immunofluorescent probes. Cells were quantified using StrataQuest digital image analysis software, with intratumoral and stromal regions analyzed separately. Kaplan-Meier estimates and Cox regression were used to assess survival.

Results: Intratumoral CD8⁺ cell density (HR = .52, 95% confidence interval [CI] .33-.83, P = .007), stromal CD11c⁺ cell density (HR = .52, 95% CI .33-.83, P = .006), intratumoral CD11c⁺ PD-L1⁺ cell density (HR = .57, 95% CI .35-.92, P = .021), and stromal CD11c⁺ PD-L1⁺ cell density (HR = .48, 95% CI .30-.77, P = .003) on leading-edge cores were all significantly associated with good survival. CD8⁺ cell density was positively correlated with both CD11c⁺ cell density and CD11c⁺ PD-L1⁺ cell density in tumor epithelium and stromal compartments.

Conclusion: Here we showed that PD-L1-expressing DC in the tumor microenvironment are associated with improved survival in stage III colon cancer and likely reflect an immunologically "hot" tumor microenvironment. Further investigation into the expression of immunomodulatory molecules by tumor-associated DC may help to further elucidate their prognostic value.

Keywords: CD8; PD-L1; T cells; colon cancer; dendritic cells.