Increase in PD-L1 expression after pre-operative radiotherapy for soft tissue sarcoma

• Type of Material: Article
• Authors: Kirtesh R. Patel, Yale University; Anthony Martinez, Emory University; John M. Stahl, Yale University; Suzanna J. Logan, Emory University; Adam J. Perricone, Emory University; Matthew J. Ferris, Emory University; Zachary S. Buchwald, Emory University; Mudit Chowdhary, Emory University; Keith A Delman, Emory University; David K Monson, Emory University; Shervin Oskouei, Emory University; Nickolas B. Reimer, Emory University; Ken Cardona, Emory University; Mark Allen Edgar, Emory University; Karen D Godette, Emory University
• Language: English
• Date: 2018-01-01
• Publisher: Taylor & Francis: STM, Behavioural Science and Public Health Titles
• Publication Version: Final Published Version
• Copyright Statement: © 2018 The Author(s). Published with license by Taylor & Francis Group, LLC © 2018, © Kirtesh R. Patel, Anthony Martinez, John M. Stahl, Suzanna J. Logan, Adam J. Perricone, Matthew J. Ferris, Zachary S. Buchwald, Mudit Chowdhary, Keith A. Delman, David K. Monson, Shervin V. Oskouei, Nicholas B. Reimer, Kenneth Cardona, Mark A. Edgar and Karen D. Godette.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1080/2162402X.2018.1442168
• Title of Journal or Parent Work: OncoImmunology
• ISSN: 2162-4011
• Volume: 7
• Issue: 7
• Start Page: e1442168
• End Page: e1442168
• Keywords: Science & Technology; PHASE-1 TRIAL; Radiation; MELANOMA; Immunology; Immunotherapy; PEMBROLIZUMAB; Soft Tissue Sarcoma; PD-L1; Oncology; BLOCKADE; ACQUIRED-RESISTANCE; CELL LUNG-CANCER; Life Sciences & Biomedicine; IMMUNOTHERAPY
• Research Categories: Health Sciences, Radiology; Health Sciences, Oncology

Abstract

Soft tissue sarcomas (STS) have minimal expression of PD-L1, a biomarker for PD-1 therapy efficacy. Radiotherapy (RT) has been shown to increase PD-L1 expression pre-clinically. We examined the expression of PD-L1, pre- and post-RT, in 46 Stage II-III STS patients treated with pre-operative RT (50–50.4 Gy in 25–28 fractions) followed by resection. Five additional patients who did not receive RT were utilized as controls. PD-L1 expression on biopsy and resection samples was evaluated by immunochemistry using the anti PD-L1 monoclonal antibody (E1L3 N clone; Cell Signaling). Greater than 1% membranous staining was considered positive PD-L1 expression. Changes in PD-L1 expression were analyzed via the Fisher exact test. Kaplan-Meier statistics were used to correlate PD-L1 expression to distant metastases (DM) rate. The majority of STS were T2b (87.0%), high-grade (80.4%), undifferentiated pleomorphic histology (71.7%), and originated from the extremities (84.6%). Zero patients demonstrated PD-L1 tumor expression pre-RT. Post-RT, 5 patients (10.9%) demonstrated PD-L1 tumor expression (p = 0.056). Tumor associated macrophages (TAM) expression of PD-L1 increased after RT: 15.2% to 45.7% (p = 0.003). Samples from controls demonstrated no baseline (0%) or change in tumor PD-L1 expression. Freedom from DM was lower for patients with PD-L1 TAM expression post-RT (3 years: 49.7% vs. 87.8%, log-rank p = 0.006); TAM PD-L1 positivity remained an independent predictor for DM on multivariate analyses (Hazard ratio–0.16, 95% confidence interval: 0.034–0.721, p = 0.042). PD-L1 expression on human STS tumor and TAM appears to elevate after pre-operative RT. Expression of PD-L1 on TAM after RT was associated with a higher rate of DM.