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Author Notes:

CONTACT Kirtesh R. Patel, MD kirtesh.patel@yale.edu Department of Therapeutic Radiology, Yale School of Medicine, 333 Cedar Street, Smilow Cancer Building, Lower Level, Room 511, New Haven, Connecticut 06511, USA; Mudit Chowdhary, MD mchowdharymd@gmail.com Department of Radiation Oncology, Emory University School of Medicine, 1365 Clifton Road NE, Room AT225, Atlanta, GA, 30322, USA.

No potential conflicts of interest were disclosed.

Subjects:

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Oncology
  • Immunology
  • Soft Tissue Sarcoma
  • PD-L1
  • Immunotherapy
  • Radiation
  • CELL LUNG-CANCER
  • ACQUIRED-RESISTANCE
  • PHASE-1 TRIAL
  • PEMBROLIZUMAB
  • MELANOMA
  • IMMUNOTHERAPY
  • BLOCKADE

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

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Journal Title:

OncoImmunology

Volume:

Volume 7, Number 7

Publisher:

, Pages e1442168-e1442168

Type of Work:

Article | Final Publisher PDF

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.

Copyright information:

© 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.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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