Expression of PD-L1 and other immunotherapeutic targets in thymic epithelial tumors Journal Article

Authors: Arbour, K. C.; Naidoo, J.; Steele, K. E.; Ni, A.; Moreira, A. L.; Rekhtman, N.; Robbins, P. B.; Karakunnel, J.; Rimner, A.; Huang, J.; Riely, G. J.; Hellmann, M. D.
Article Title: Expression of PD-L1 and other immunotherapeutic targets in thymic epithelial tumors
Abstract: Introduction: The thymus is a critical organ for the development of the adaptive immune system and thymic epithelial tumors (TETs; thymomas and thymic carcinomas) are often associated with auto-immune paraneoplastic conditions. However, the immunobiology of TETs is not well described. An evaluation of the tumor microenvironment, with particular focus on expression of immunotherapeutic targets, may facilitate and prioritize development of immunotherapy strategies for patients with TETs. Methods: Tumor tissues from 23 patients with WHO Type B2/B3 thymoma (n = 12) and thymic carcinoma (n = 11) were identified and clinical outcomes were annotated. The expression of membranous PD-L1 on tumor cells, CD3+ and CD8+ tumor infiltrating lymphocytes (TILs), co-stimulatory (CD137, GITR, ICOS), and co-inhibitory immune checkpoint molecules (PD-1, CTLA-4, TIM-3) were assessed semi-quantitatively using immunohistochemistry. Results: PD-L1 positivity ( 25% of tumor membrane expression) was frequent in TETs (15/23, 65%), more common in thymomas compared to thymic carcinomas (p<0.01), and was associated with longer overall survival (p = 0.02). TIM-3 and GITR were expressed in all TETs, including 18/23 and 12/23 with at least moderate/high expression, respectively. Moderate/high CD137 expression correlated with CD8+ (p = 0.01) and moderate/high GITR expression co-associated with PD-1 (p = 0.043). Conclusions: TETs are characterized by frequent PD-L1 expression and PD-L1 is associated with improved survival, suggesting PD-L1 signaling may be biologically important in TETs. Robust expression of markers of immune activation and immunotherapeutic target molecules in TETs emphasizes the potential for development of anti-PD-1/PD-L1 therapies. © 2017 Arbour et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Journal Title: PLoS ONE
Volume: 12
Issue: 8
ISSN: 1932-6203
Publisher: Public Library of Science  
Date Published: 2017-08-03
Start Page: e0182665
Language: English
DOI: 10.1371/journal.pone.0182665
PROVIDER: scopus
PMCID: PMC5542609
PUBMED: 28771603
Notes: Article -- Export Date: 5 September 2017 -- Source: Scopus
Citation Impact
MSK Authors
  1. Natasha Rekhtman
    338 Rekhtman
  2. Andre L Moreira
    175 Moreira
  3. James Huang
    155 Huang
  4. Gregory J Riely
    487 Riely
  5. Andreas Rimner
    397 Rimner
  6. Matthew David Hellmann
    348 Hellmann
  7. Jarushka Naidoo
    33 Naidoo
  8. Ai   Ni
    96 Ni
  9. Kathryn Cecilia Arbour
    58 Arbour