Targeting PD-L1 initiates effective antitumor immunity in a murine model of Cushing disease

Hanna R. Kemeny, Aladine A. Elsamadicy, S. Harrison Farber, Cosette D. Champion, Selena J. Lorrey, Pakawat Chongsathidkiet, Karolina I. Woroniecka, Xiuyu Cui, Steven H. Shen, Kristen E. Rhodin, Vadim Tsvankin, Jeffrey Everitt, Luis Sanchez-Perez, Patrick Healy, Roger E. McLendon, Patrick J. Codd, Ian F. Dunn, Peter E. Fecci

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)1141-1151
Number of pages11
JournalClinical Cancer Research
Volume26
Issue number5
DOIs
StatePublished - Mar 1 2020

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