Increase in PD-L1 expression after pre-operative radiotherapy for soft tissue sarcoma. (3rd July 2018)

• Record Type: Journal Article
• Authors: Patel, Kirtesh R.; Martinez, Anthony; Stahl, John M.; Logan, Suzanna J.; Perricone, Adam J.; Ferris, Matthew J.; Buchwald, Zachary S.; Chowdhary, Mudit; Delman, Keith A.; Monson, David K.; Oskouei, Shervin V.; Reimer, Nicholas B.; Cardona, Kenneth; Edgar, Mark A.; Godette, Karen D.
• Is Part Of: Oncoimmunology. Volume 7:Number 7(2018)
• Publication Date: 2018-07-03
• Subjects: Soft Tissue Sarcoma -- PD-L1 -- Immunotherapy -- Radiation; Tumors -- Immunological aspects -- Periodicals; Neoplasms -- therapy -- Periodicals; Immunotherapy -- Periodicals; 616.994
• DOI: 10.1080/2162402X.2018.1442168
• Languages: English
• ISSNs: 2162-402X

Abstract

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.