Oncotarget

Research Papers:

PD-L1 expression on immune cells is a favorable prognostic factor for vulvar squamous cell carcinoma patients

Jacek J. Sznurkowski _, Anton Żawrocki, Katarzyna Sznurkowska, Rafał Pęksa and Wojciech Biernat

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Oncotarget. 2017; 8:89903-89912. https://doi.org/10.18632/oncotarget.20911

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Abstract

Jacek J. Sznurkowski1, Anton Żawrocki2, Katarzyna Sznurkowska3, Rafał Pęksa2 and Wojciech Biernat2

1Department of Oncological Surgery, The Medical University, Gdańsk, Poland

2Department of Pathology, The Medical University, Gdańsk, Poland

3Department of Pediatrics, Pediatric Gastroenterology, Hepathology and Nutrition, The Medical University, Gdańsk, Poland

Correspondence to:

Jacek J. Sznurkowski, email: jacek.sznurkowski@gumed.edu.pl

Keywords: vulvar SCC, PD-L1, HPV, p16, prognosis

Received: July 13, 2017    Accepted: August 29, 2017    Published: September 15, 2017

ABSTRACT

Background: Anti-immune programmed death-ligand 1 (PD-L1) pathway is used by the tumor to overcome immune system and serves as immunotherapy target in various malignancies.

Aim: To investigate the expression of PD-L1 in vulvar squamous cell carcinoma (vSCC) and to assess it’s clinicopathological and prognostic significance.

Methods: Immunohistochemical PD-L1 expression was evaluated in 84 vSCCs with previously defined status of p16 and DNA-HPV, infiltration of immune cells: CD8+, CD4+, FOXP3+, CD56+, CD68+, and GZB+ cells. PD-L1 positivity was defined as ≥5% of PD-L1-positive cells. Survival analyses included the Kaplan–Meier method, log-rank test and Cox proportional hazards model.

Results: PD-L1 expression was detected on cancer and peritumoral immune cells. PD-L1-positivity of cancer nests (27/84, 32.1%) was correlated with higher infiltration of CD4+ (p=0.037), CD8+ (p=0.02), FOXP3+ (p=0.007), CD68+ (p=0.021) cells, while PD-L1 positivity of peritumoral immune cells (51/84, 60.7%) was correlated with higher infiltration of intraepithelial FOXP3+ cells only (p=0.037).

PD-L1-positivity of cancer cells but not immune cells, was more frequently observed in p16-negative tumors (p=0.004). High-risk HPV-status did not correlate with the PD-L1 status of cancer and immune cells (p=1.000) and (p=1.000) respectively). Median follow up was 89.20 months (range 1.7-189.5). PD-L1 positivity of peritumoral immune cells was found to be an independent favorable prognostic factor for OS. Conclusion: This study highlights the importance of comprehensive PD-L1 assessment in both cancer and immune cells. PD-L1 expression on peritumoral immune cells seems to be an additional prognostic factor in vSCC patients and may influence the results by anti-PD-L1 treatment.


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