Increased expression of programmed death ligand 1 (PD L1) in human pituitary tumors
Purpose Subsets of pituitary tumors exhibit an aggressive clinical courses and recur despite surgery, radiation, and chemotherapy. Because modulation of the immune response through inhibition of T cell checkpoints has led to durable clinical responses in multiple malignancies, we explored whether pituitary adenomas express immune related biomarkers that could suggest suitability for immunotherapy. Specifically, programmed death ligand 1 (PD L1) has emerged as a potential biomarker whose expression may portend more favorable responses to immune checkpoint blockade therapies. We thus investigated the expression of PD L1 in pituitary adenomas. Methods PD L1 RNA and protein expression were evaluated in 48 pituitary tumors, including functioning and non functioning adenomas as well as atypical and recurrent tumors. Tumor infiltrating lymphocyte populations were also assessed by immunohistochemistry. Results Pituitary tumors express variable levels of PD L1 transcript and protein. PD L1 RNA and protein expression were significantly increased in functioning (growth hormone and prolactin expressing) pituitary adenomas compared to non functioning (null cell and silent gonadotroph) adenomas. Moreover, primary pituitary adenomas harbored higher levels of PD L1 mRNA compared to recurrent tumors. Tumor infiltrating lymphocytes were observed in all pituitary tumors and were positively correlated with increased PD L1 expression, particularly in the functional subtypes. Conclusions Human pituitary adenomas harbor PD L1 across subtypes, with significantly higher expression in functioning adenomas compared to non functioning adenomas. This expression is accompanied by the presence of tumor infiltrating lymphocytes. These findings suggest the existence of an immune response to pituitary tumors and raise the possibility of considering checkpoint blockade immunotherapy in cases refractory to conventional management.
Oncotarget