Avaliação da expressão gênica de CD39, CD73 e PD-l1 no tecido tumoral de pacientes com tumores neuroendócrinos hipofisários

Abstract

Pituitary neuroendocrine tumors (PitNETs), also known as pituitary adenomas, although predominantly benign, can exhibit aggressive behavior and invasiveness, hindering therapeutic success. The tumor microenvironment (TME), through the purinergic pathway (CD39 and CD73) and immune checkpoints (PD-L1), plays a pivotal role in immune escape; however, this dynamic remains underexplored in these neoplasms. The aim of this study was to evaluate the gene expression of CD39, CD73, and PD-L1 in the tumor tissue of patients with PitNETs and to correlate these expression levels with the degree of invasiveness. This is a quantitative, cross-sectional, observational study including 19 patients from Southern Brazil who underwent surgical resection between May 23, 2023 to July 8, 2025. Tumor extension was classified according to the revised Knosp grading system into low-grade (grades 0, 1 and 2) and high-grade (grades 3 and 4) invasion. Relative quantification of gene expression within the TME was performed using qRT-PCR. As results, a significantly higher expression of CD73 was found in the high-grade invasion group (p = 0.0240). Correlation analysis revealed a significant positive association between CD39 and CD73 (r = 0.5542; p = 0.0170). In conclusion, the invasive phenotype of PitNETs is strongly associated with the coordinated activation of the purinergic pathway, which appears to be driven independently of the PD-1/PD-L1 axis. The ectonucleotidase CD73 emerges as a potential biomarker for tumor aggressiveness and a promising therapeutic target for immunotherapy in PitNETs.