Targeting PD-L1 initiates effective anti-tumor immunity in a murine model of Cushing's Disease

Purpose: Though pituitary adenoma is classified as benign, CD is associated with significant morbidity due to the numerous sequelae of elevated cortisol levels. Successful therapy for CD 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 Cushing9s Disease (CD). Results: Herein, treatment with anti-PD-L1 was successful in reducing ACTH 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 CD. Clinical investigation is encouraged.