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PD-L1 expression is an unfavourable prognostic indicator in Asian renal cell carcinomas
  1. Joe Yeong1,2,
  2. Zitong Zhao2,
  3. Jeffrey Chun Tatt Lim1,3,
  4. Huihua Li4,5,
  5. Aye Aye Thike3,
  6. Valerie Cui Yun Koh3,
  7. Bin Tean Teh6,7,
  8. Ravindran Kanesvaran8,9,
  9. Chee Keong Toh9,
  10. Puay Hoon Tan2,3,8,
  11. Li Yan Khor2,8
  1. 1Institute of Molecular Cell Biology (IMCB), Agency of Science, Technology and Research (A*STAR), Singapore, Singapore
  2. 2Anatomical Pathology, Singapore General Hospital, Singapore, Singapore
  3. 3Pathology, Singapore General Hospital, Singapore, Singapore
  4. 4Center for Quantitative Medicine, Duke-NUS Medical School, Singapore, Singapore
  5. 5Division of Medicine, Singapore General Hospital, Singapore, Singapore
  6. 6Laboratory of Cancer Epigenome, National Cancer Centre, Singapore, Singapore
  7. 7Division of Cancer and Stem Cell Biology, Duke-NUS Graduate Medical School, Singapore, Singapore
  8. 8Dean's Office, Duke-NUS Medical School, Singapore, Singapore
  9. 9National Cancer Centre Singapore, Singapore, Singapore
  1. Correspondence to Dr Li Yan Khor, Pathology, Singapore General Hospital, Singapore, Singapore; khor.li.yan{at}singhealth.com.sg

Abstract

Background/aims The programmed cell death receptor 1 (PD-1) checkpoint inhibitor, nivolumab, has been approved for the treatment of metastatic renal cell carcinoma (RCC). However, the understanding of the expression and distribution of PD ligand 1 (PD-L1) in the tumour immune microenvironment and its prognostic role in an Asian cohort is limited. Our group investigated PD-L1 protein expression in a cohort of Asian patients with RCC of mixed ethnicity, using two commercially available antibody clones.

Methods E1L3N and SP263 anti-PD-L1 clones were used to categorise RCCs of various histological subtypes, diagnosed at our institution between 1995 and 2008, into PD-L1-positive or PD-L1-negative groups, based on a 1% Tumour Proportion Score (TPS) cut-off.

Results In total, 267 (83%) clear cell (cc)RCC and 55 (17%) non-ccRCC cases were studied. Overall PD-L1 protein expression rates for the entire cohort were 13% and 8% for the E1L3N and SP263 clones, respectively. Patients bearing PD-L1-positive tumours experienced significantly decreased disease-free survival (DFS; E1L3N: p=0.01; SP263: p=0.03) but not overall survival, compared with those with PD-L1-negative tumours. Multivariate survival analysis further confirmed the results of the E1L3N clone (HR 1.85, 95% CI 1.10 to 3.13, p=0.02), but not SP263, after adjusting for pathological stage, histological subtype and grade. The addition of PD-L1 (E1L3N) TPS to clinicopathological features significantly increased the prognostic value for DFS (∆LRχ2=5.25; p=0.022), compared with clinicopathological features alone.

Conclusions PD-L1 protein expression was associated with an unfavourable prognosis in our study cohort. PD-L1 (E1L3N) expression was an independent prognostic indicator of clinical outcome in all RCCs when using a 1% cut-off.

  • uropathology
  • immunopathology
  • oncology
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Footnotes

  • Handling editor Dhirendra Govender.

  • JY and ZZ contributed equally.

  • Contributors The study was designed and directed by LYK and PHT, and coordinated by JY. JY, ZZ, JCTL, AAT and VCYK acquired the data. The analysis was done by HL. CKT, BTT and RK provided advice from clinical perspectives. JY and LYK drafted the manuscript, which was commented on and revised by all authors.

  • Funding This research was funded by the Centre Grant (CG) grant of Singapore General Hospital (NMRC/CG/M011/2017_SGH).

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval The Centralised Institutional Review Board of SingHealth approved the use of patient materials in the present study (CIRB Ref: 2005/001/F).

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement All data relevant to the study are included in the article or uploaded as online supplementary information.

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