Abstract
PurposeSubsets 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.MethodsPD-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.ResultsPituitary 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.ConclusionsHuman 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.
Highlights
Pituitary tumors are the second most common intracranial neoplasms, comprising 10-15% of diagnosed brain tumors [1, 2]
Primary pituitary adenomas harbored higher levels of programmed death ligand 1 (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, in the functional subtypes
Summary
Pituitary tumors are the second most common intracranial neoplasms, comprising 10-15% of diagnosed brain tumors [1, 2]. Some pituitary tumors are considered “functioning” and liberate physiologic hormones to a pathologic degree to manifest as one of several classic endocrinologic syndromes. Other pituitary tumors are hormonally silent (non-functioning) but may compress adjacent neurovascular structures during growth, conferring degrees of visual loss, pituitary dysfunction, and cranial neuropathies. Often cured by surgery alone or controlled medically, as in the case of most prolactin-secreting tumors, recurrence rates are not insignificant. In a large cohort of patients followed for 10 years after transsphenoidal surgery, rates of recurrence across tumor subtypes varied between 6-25% [3]. Adjuvant medical treatments in functioning and non-functioning tumors are only variably effective in durable tumor control, and radiotherapy may be limited by proximity to the optic nerves. There are a limited number of adjuvant treatment options for clinically challenging pituitary tumors
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
