Checkpoint molecule PD-1-assisted CD8+ T lymphocyte count in tumor microenvironment predicts overall survival of patients with metastatic renal cell carcinoma treated with tyrosine kinase inhibitors.

Abstract

PurposeThe aim of this study was to determine whether CD8+ T lymphocyte and its checkpoint-associated module programmed cell death protein 1 (PD-1)/main ligand of PD-1 (PD-L1) pathway impact overall survival (OS) in patients with metastatic renal cell carcinoma (mRCC) treated with tyrosine kinase inhibitors (TKIs).Materials and methodsA total of 231 mRCC patients, from 2007 to 2017, treated with sunitinib or sorafenib in Zhongshan Hospital, Fudan University were included in the study analyses. CD8, PD-1, and PD-L1 was assessed by immunohistochemistry on continuous paraffin-embedded slides. Kaplan–Meier method and COX regression model were applied in the survival analyses.ResultsBaseline characteristics were comparable between the training (n=118) and validation (n=113) sets. Patients with high CD8+ T lymphocytes infiltration and low PD-1 expression had longer survival in both sets (P=0.0106 and P=0.0047 in training set, P=0.0291 and P=0.0011 in validation set, respectively). However, survival stratified by PD-L1 was only insignificant or marginally significant. Multivariable analyses verified that CD8+ T lymphocytes, together with PD-1, but not tumor infiltrating mononuclear cells or tumor cells PD-L1, were independent prognostic factors (training set [HR 3.202, 95% CI 1.433–7.153, P=0.011] and validation set [HR 4.012, 95% CI 2.354–6.838, P<0.001]). Subsequent analysis revealed that the PD-1 high/CD8 low group had shorter survival (16 months) than PD-1 low/CD8 high group (51 months, P<0.0001). Combining the International Metastatic Renal Cancer Database Consortium system with the PD-1/CD8 model exhibited much better accuracy for the prediction of OS.ConclusionOur findings suggest that abundant CD8+ T cells are significantly associated with longer OS in mRCC patients treated with TKIs. The most influential checkpoint-associated molecule, PD-1, assisted CD8+ T cell-stratified patients and could be used as a better predictive and prognostic factor for the mRCC patients.