Targeting PD-L1 Initiates Effective Antitumor Immunity in a Murine Model of Cushing Disease.

Journal Article (Journal Article)

PURPOSE: Although pituitary adenoma is classified as benign, Cushing disease is associated with significant morbidity due to the numerous sequelae of elevated cortisol levels. Successful therapy for Cushing disease remains elusive due to high rates of treatment-refractory recurrence. The frequent emergence of lymphocytic hypophysitis following checkpoint blockade for other cancers, as well as the expression of PD-L1 on pituitary adenomas, suggest a role for immunotherapy. EXPERIMENTAL DESIGN: This study confirms PD-L1 expression on functioning pituitary adenomas and is the first to evaluate the efficacy of checkpoint blockade (anti-PD-L1) therapy in a preclinical model of Cushing disease. RESULTS: Herein, treatment with anti-PD-L1 was successful in reducing adrenocorticotropic hormone plasma levels, decreasing tumor growth, and increasing survival in our model. Furthermore, tumor-infiltrating T cells demonstrated a pattern of checkpoint expression similar to other checkpoint blockade-susceptible tumors. CONCLUSIONS: This suggests that immunotherapy, particularly blockade of the PD1/PD-L1 axis, may be a novel therapeutic option for refractory Cushing disease. Clinical investigation is encouraged.

Full Text

Duke Authors

Cited Authors

  • Kemeny, HR; Elsamadicy, AA; Farber, SH; Champion, CD; Lorrey, SJ; Chongsathidkiet, P; Woroniecka, KI; Cui, X; Shen, SH; Rhodin, KE; Tsvankin, V; Everitt, J; Sanchez-Perez, L; Healy, P; McLendon, RE; Codd, PJ; Dunn, IF; Fecci, PE

Published Date

  • March 1, 2020

Published In

Volume / Issue

  • 26 / 5

Start / End Page

  • 1141 - 1151

PubMed ID

  • 31744830

Pubmed Central ID

  • 31744830

Electronic International Standard Serial Number (EISSN)

  • 1557-3265

Digital Object Identifier (DOI)

  • 10.1158/1078-0432.CCR-18-3486

Language

  • eng

Conference Location

  • United States