Endocrine Abstracts

Recent studies have reported that tissue micro-environment including tumor infiltrating lymphocytes (TILs) as well as neo-angiogenesis played pivotal roles in biological and clinical behavior of various human malignancies. In adrenal neoplasms, TILs are far more frequently detected in cortical than medullary tumors. In adrenocortical adenomas, we have recently demonstrated that enhanced angiogenic chemokines, especially CXCL12, in cortisol producing adenoma (CPA), induced TILs, especially CXCR4 positive T cells, which are involved in removing tumor cells of CPA harboring DNA damages inflicted by excessive cortisol through promoting cell senescence from tumor microenviroment. In adrenocortical carcinoma (ACC), PD-1 receptor and its ligand, PD-L1 have been considered to play pivotal roles in immune checkpoint mechanism and to serve as potential markers responding to immunotherapy in various human cancers. In ACC, however, conflicting results have been reported and recent clinical trials of the agent targeting PD-L1 also provided lukewarm results in terms of therapeutic outcome of ACC patients. In TILs, recent study demonstrated the better clinical outcome in the pediatric ACC patients harboring a high CD8 + -CTL count. In our recent study of adult ACC cases, CD8 count was significantly correlated with TILs but also with CD4 and Treg or FOXP3 counts. PDL-1 status in carcinoma cells of ACC , was also significantly correlated with TILs and CD8 counts but also with CD4 count in the tumor and PD-L1 positive carcinoma cells were less than 1% in all 15 cases examined. In pheochromocytoma, results of our recent study in 39 cases revealed that TILs were not as abundant as other malignancies but CD8 counts as well as vascularity examined by CD31 positive endothelial cells served as the prognostic factors in well differentiated pheochromocytoma. In addition, as previously reported, CD68/CD163 positive macrophages appeared to play roles in biological behavior of well differentiated pheochromocytoma.