EXPRESSION PATTERNS OF ESTROGEN AND ANDROGEN RECEPTORS IN NSCLC PATIENTS ACCORDING TO THE PD-L1 PROFILE

Vianey Rodriguez-Lara^1*Gala Cortés-Ramírez¹Itzel Amayrani Angeles-Torres¹Jeronimo Rodriguez-Cid²Sally María Luisa Pedraza-Reyes²Maria Rosa Avila-Costa¹Heriberto Prado-Garcia²José Luis Ordoñez-Librado¹MA Cerbon¹

• ¹National Autonomous University of Mexico, México City, Mexico
• ²National Institute of Respiratory Diseases-Mexico (INER), Mexico City, México, Mexico

Background: Lung cancer is the leading cause of cancer-related death worldwide, with non-small cell lung cancer (NSCLC) being the most common type. Immunotherapy targeting programmed death ligand-1 (PD-L1) blockade has significantly improved survival, but differences in responses by sex have been reported, suggesting a possible role of sex hormones. Estrogens and androgens, through their receptors support lung carcinogenesis, but their role in immune evasion via the PD-1/PD-L1 pathway remains poorly understood.We analyzed by immunohistochemistry the expression patterns of estrogen receptors (ERa and ERb) and androgen receptor (AR) in 95 PD-L1-positive (PD-L1+) and 72 PD-L1 negative (PD-L1-) NSCLC patients by sex and hormonal status. We also investigated associations between hormonal receptors, PD-L1 profile, PD-L1 tumor proportion score (TPS), and clinical features (cancer stage according to the TNM stage of cancer, smoking history, wood smoke exposure, and asbestos exposure).Results: ERb was the predominant form of estrogen receptor in PD-L1-patients, while ERa expression was significantly higher in PD-L1+ patients and strongly associated with the PD-L1+ profile, regardless of sex or hormonal status. AR expression was low across all groups and showed no association with PD-L1. Among PD-L1+ patients, ERα expression levels were highest in premenopausal women, followed by men and postmenopausal women. ERa levels in the PD-L1+ group, were not associated with PD-L1 TPS or with clinical features.The estrogen pathway, particularly via ERa, plays a key role in PD-L1 expression and may contribute to tumor immune evasion. Antiestrogen therapy could represent a promising strategy to enhance immunotherapy efficacy in patients expressing ERs.