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Targeting PD-L1 Initiates Effective Antitumor Immunity in a Murine Model of Cushing Disease.
- Source :
-
Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2020 Mar 01; Vol. 26 (5), pp. 1141-1151. Date of Electronic Publication: 2019 Nov 19. - Publication Year :
- 2020
-
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.<br />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.<br />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.<br />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.<br /> (©2019 American Association for Cancer Research.)
- Subjects :
- Adenoma drug therapy
Adenoma immunology
Adenoma pathology
Adolescent
Adult
Aged
Aged, 80 and over
Animals
Cell Line, Tumor
Disease Models, Animal
Female
Humans
Male
Mice
Mice, Inbred C57BL
Middle Aged
Pituitary ACTH Hypersecretion immunology
Pituitary ACTH Hypersecretion pathology
Pituitary Neoplasms immunology
Pituitary Neoplasms pathology
Survival Rate
Young Adult
Antibodies, Monoclonal pharmacology
B7-H1 Antigen antagonists & inhibitors
B7-H1 Antigen metabolism
Immunotherapy methods
Pituitary ACTH Hypersecretion drug therapy
Pituitary Neoplasms drug therapy
T-Lymphocytes immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1557-3265
- Volume :
- 26
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Clinical cancer research : an official journal of the American Association for Cancer Research
- Publication Type :
- Academic Journal
- Accession number :
- 31744830
- Full Text :
- https://doi.org/10.1158/1078-0432.CCR-18-3486