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Comparative Study
, 123 (24), 4823-4831

Programmed Cell Death Ligand 1 and Tumor-Infiltrating Lymphocyte Status in Patients With Renal Cell Carcinoma and Sarcomatoid Dedifferentiation

Affiliations
Comparative Study

Programmed Cell Death Ligand 1 and Tumor-Infiltrating Lymphocyte Status in Patients With Renal Cell Carcinoma and Sarcomatoid Dedifferentiation

Fumi Kawakami et al. Cancer.

Abstract

Background: The immune profile of sarcomatoid renal cell carcinoma (sRCC), including the programmed cell death ligand 1 (PD-L1) and programmed cell death 1 (PD-1) status, has not been well characterized.

Methods: An immunohistochemical digital analysis of PD-L1, PD-1, CD4, and CD8 was performed on nephrectomy specimens from 118 sRCC patients and 92 nonsarcomatoid clear cell renal cell carcinoma (ccRCC) patients. The clinical characteristics of the population were compared between sRCC and ccRCC. Overall survival was estimated, and comparisons were made between PD-L1-positive and PD-L1-negative groups as well as tumor-infiltrating lymphocyte (TIL)-high and TIL-low groups.

Results: The PD-L1 H-score of sRCC (mean, 3.7; range, 0-192.1) was significantly higher than the score of grade 4 ccRCC (P = .001), and 41.3% of sRCC cases showed a PD-L1 H-score ≥ 10. The PD-1-positive cell density was significantly higher in sRCC versus ccRCC within the tumor and at the invasive front. The intratumoral CD8-positive cell density was significantly higher in sRCC versus ccRCC. Forty-one percent in the sarcomatoid component of sRCC and 8% in the epithelioid component of sRCC had an adaptive immune resistance phenotype (PD-L1-positive and TIL-positive), whereas only 1% in ccRCC had the type I phenotype.

Conclusions: sRCC showed higher PD-L1 expression and higher PD-1- and CD8-positive cell density than grade 4 ccRCC. The results indicate a notable immunosuppressive environment in sRCC. Despite advances in the treatment of advanced-stage renal cell carcinoma, sRCC still has a poor prognosis. This work describes highly immunosuppressive characteristics of sRCC in comparison with an appropriate ccRCC control. The results suggest PD-1/PD-L1 blockade therapy as a potential therapeutic approach for sRCC. Cancer 2017;123:4823-31. © 2017 American Cancer Society.

Keywords: immunotherapy; programmed cell death 1 (PD-1); programmed cell death ligand 1 (PD-L1); renal cell carcinoma; sarcomatoid renal cell carcinoma.

Conflict of interest statement

Conflicts of interest: JAK has acted as a consultant/advisory board member for Pfizer, EMD Serono, Novartis. No conflict of interest related to this work/manuscript.

Figures

Figure 1
Figure 1
PD-L1 immunohistochemical staining in patients with sRCC. Membranous staining is present in the sarcomatoid tumor component (A) and the epithelioid component (B). (C) In this case, only tumor-infiltrated macrophages and lymphocytes showed weak to moderate cytoplasmic positivity.
Figure 2
Figure 2
Correlation of PD-L1 expression level and overall survival in the sarcomatoid component of sRCC. A cutoff H-score of ≥10 showed good correlation with manual immunohistochemical evaluation results but not with overall survival
Figure 3
Figure 3
Tumor PD-L1 expression and infiltrating PD-1–positive cells status in clear cell sarcomatoid and non-sarcomatoid ccRCC. (A) PD-L1 expression in the sarcomatoid component of sRCC was significantly higher than in the epithelioid component and in Fuhrman grades 2, 3, and 4 pure epithelioid ccRCC. Although there was no difference in PD-1–positive cell density in the intratumoral region (B) or in the peritumoral region (C) between the sarcomatoid component and the epithelioid component in sRCC, both components had higher PD-1–positive cell density in both areas than Fuhrman grades 2, 3 and 4 pure epithelioid RCC. Sarc; sarcomatoid component, Ep; epithelioid component.

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