Background Pituitary tumors are the second most common primary brain tumors. We previously demonstrated
that hormone-secreting, or functional, adenomas may host a suppressed immune surveillance
state, as evidenced by increased expression of the immune checkpoint marker PD-L1.
We hypothesized that pituitary adenomas exhibit a variable immune signature which
may influence their behavior, and sought to profile an expanded cohort of immune regulatory
markers to better characterize their immune microenvironment.
Method Seventy-two pituitary adenomas were evaluated for expression of the immune regulatory
markers PD-L1, VISTA, and OX40 by immunohistochemistry, as well as for lymphocytes
infiltration by the T cell markers CD8 and FOXP3, and the macrophage markers CD163,
CD68, and CD45. LAG3, a marker of T cell exhaustion was also assessed.
Results We observed a prominent immune cell infiltrate, as defined by high expression of
T cell or macrophage markers, in 40% of tumors. In addition, we observed high expression
of the immune regulatory markers, PD-L1, VISTA, LAG3, and OX40 in 60% of adenomas.
Interestingly, these markers were differentially elevated in different subset of tumors,
with near exclusivity between those adenomas with high expression of OX40 and VISTA.
Forty percent of the adenomas were functional tumors; 11% were recurrent. Extent of
macrophage infiltration was comparable between functional and nonfunctional adenomas.
T cell infiltration, as indicated by CD8 and FOXP3 expression, was significantly increased
in functional tumors with increased expression of the T cell exhaustion marker LAG3.
In addition, functional adenomas had increased expression of the negative immune checkpoint
regulators, PD-L1 and VISTA, along with reduced expression of the T cell activation
marker OX40. Within functional adenomas, PD-L1 correlated to the T regulatory cell
marker FOXP3, while expression of VISTA correlated with the macrophage marker CD68.
Primary adenomas expressed higher level of PD-L1 and LAG3 compared with recurrent
adenomas.
Conclusion We demonstrate a significant and variable presence of immune infiltrates and regulatory
proteins within pituitary adenomas. Immune escape was more prominent in functional
and primary pituitary adenomas. The presence of different immune checkpoint markers
in distinct pituitary adenoma populations calls for novel therapeutic strategies that
account for such diversity of immune regulation.
