PD-L1 expression patterns in tumour cells and their association with CD8+ tumour infiltrating lymphocytes in clear cell renal cell carcinoma

J Cancer. 2019 Jan 29;10(5):1154-1161. doi: 10.7150/jca.29052. eCollection 2019.

Abstract

Purpose: To evaluate the tumour cell PD-L1 (TC-PD-L1) expression patterns in the local microenvironment of clear cell renal cell carcinoma (ccRCC). Materials and Methods: 30 fresh primary ccRCC tissues were used to detect the association between TC-PD-L1 and CD8+TILs at mRNA level. The in vitro incubation experiment was used to confirm the association between extrinsic TC-PD-L1 expression and IFNγ. A cohort of 135 ccRCC patients treated between January 2009 and August 2013 was included for survival analysis. Results: Our results confirmed that ccRCC cell lines were capable of expressing PD-L1. The incubation experiment in vitro demonstrated the positive correlation of TC-PD-L1 expression with interferon-gamma (IFNγ). Additionally, survival analysis was investigated in 135 ccRCC patients and found no independent correlation of TC-PD-L1 expression in multivariate analysis, whereas more distinct prognostic differences were detected when TC-PD-L1-positive ccRCC were sub-classified as with or without CD8+ T cell infiltration. Conclusion: The intrinsic and extrinsic expression patterns are both detected in ccRCC. High positive rate of TC-PD-L1 correlated closely to the strong infiltration of CD8+ TILs. TC-PD-L1-positive ccRCC patients with abundant CD8+ TILs infiltration confer the high risk of death and disease relapse.

Keywords: PD-L1; clear cell renal cell carcinoma; extrinsic expression; intrinsic expression; local microenvironment.