Abstract

BackgroundPD-L1 expression predicts response to immune checkpoint inhibitors in renal cell carcinomas (RCC), but has also been suggested to be linked to poor patient outcome.MethodsWe analyzed PD-L1 in > 1400 RCC in a tissue microarray format by immunohistochemistry. Results were compared with histological tumor type, parameters of cancer aggressiveness, and intratumoral CD8+ cytotoxic cells.ResultAt a cut-off level of 5% PD-L1 positive tumor cells, PD-L1 positivity was seen in 6.3% of 633 clear cell RCC (ccRCC), 18.2% of 165 papillary RCC, 18.8% of 64 chromophobe RCC, and 41.7% of 103 oncocytomas. In ccRCC, PD-L1 positivity was significantly linked to high ISUP (p < 0.0001), Fuhrman (p < 0.0001), Thoenes grade (p < 0.0001), distant metastasis (p = 0.0042), short recurrence-free (p < 0.0001), and overall survival (p = 0.0002). Intratumoral CD8+ lymphocytes were more frequent in PD-L1 positive (1055 ± 109) than in PD-L1 negative ccRCC (407 ± 28; p < 0.0001). PD-L positive immune cells were seen in 8.2% of all RCC and 13.9% of papillary RCC. In ccRCC, PD-L1 positive immune cells were linked to high numbers of tumor-infiltrating CD8+ cells (p < 0.0001), high ISUP (p < 0.0001), Fuhrman (p = 0.0027), and Thoenes grade (p < 0.0001), and poor tumor-specific survival (p = 0.0280).ConclusionsThese data suggest that PD-L1 expression in highly immunogenic RCCs facilitates immune evasion and contributes to cancer aggressiveness.

Highlights

  • Material and methodsRenal cell carcinoma (RCC) is one of the most common cancer types worldwide [1]

  • programmed cell death 1 ligand 1 (PD-L1) staining in tumor cells was often diffuse, sometimes focal within tumors and showed a mosaic pattern with a random appearing mixture of positive and negative cells

  • PD-L1 staining in tumor cells was significantly more frequent in papillary (18%) and chromophobe (19%), than in clear cell renal cell carcinomas (RCC) (6%)

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Summary

Introduction

Material and methodsRenal cell carcinoma (RCC) is one of the most common cancer types worldwide [1]. In RCC, several studies suggested that PD-L1 positivity is associated with a high number of tumor-infiltrating lymphocytes [13,14,15,16,17,18,19,20] and poor prognosis in cancers treated otherwise [15, 17, 19, 21,22,23,24,25,26,27,28,29,30,31,32].

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