Abstract 1042: MAGE-A3 and PD-L1 protein co-expression in lung cancer a look at the immune cells’ tumor microenvironment

Abstract This lab’s previous studies highlight the co-expression of PD-L1 (CD274) and MAGE-A3/A4 in non-small cell lung cancer (NSCLC) and squamous cell lung cancer, with around 50% of the screened tumors exhibiting this co-expression. Additionally, this study also identified MAGE-A3/A4 as a secreted protein using CytoSections. A sandwich ELISA was developed for MAGE-A3/A4 and demonstrated that serum levels of MAGE-A3 protein were significantly elevated in lung cancer patients compared to matched controls. This statistically significant difference suggests that MAGE-A3 could serve as a valuable biomarker for lung cancer diagnosis and prognosis. Such findings may also provide insights into the tumor microenvironment and the immune evasion mechanisms facilitated by PD-L1 and MAGE-A3 co-expression, potentially guiding the development of targeted therapies or combination strategies in the treatment of lung cancer. In this study, the lung cancers were screened with CD1C, CD163, CD20, CD31, CD3E, CD4, CD68, CD8A, FOXP3 immune markers previously evaluated with PD-L1 to characterize the tumor micro-environment where PDL1 and MAGE-A3 protein are co-expressed versus when only MAGE-A3 is expressed in lung cancer. MAGE-A3 was detected on positive CD3e and suggesting a role in regulating immune response. This study offers insights into the tumor microenvironment, a new view of immune escape in lung cancer, and the potential of MAGE-A3 as a diagnostic/prognostic biomarker and therapeutic target, particularly in combination with immune checkpoint inhibitors. Citation Format: Aimee Icaza Galarza, Rachel M. Gonzalez, YiChen Guo, Dehe Kong, Bailey Gilmore, Tianli Qu, Alex Strom, Zhaoying Guo, Qi Ren, Xiaomin Hu, Ranran Zhang, Zhaohui Wu, Jessi Chen, Xuan Liu, Wei Fu. MAGE-A3 and PD-L1 protein co-expression in lung cancer a look at the immune cells’ tumor microenvironment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1042.