Abstract 6486: Prognostic impact of the immune environment in non-small cell lung cancer

Abstract Lung cancer is the most frequent tumor related reason for death worldwide. It is hoped that a better understanding of the immune environment can foster the development of new immune checkpoint therapies to improve patient management and survival. To study the composition and prognostic impact of the immune infiltrate in non-small cell lung cancer, a tissue microarray containing 798 lung cancer patients, including 441 lung adenocarcinomas, 219 squamous cell carcinomas, was analyzed by multiplex fluorescence immunohistochemistry. A set of 14 antibodies was used to detect cytotoxic-, T-helper- and regulatory T-cells, B-cells, M2 macrophages, and dendritic cells (CD3, CD4, CD8, FOXP3, CD20, CD11c, CD163) expression of immune checkpoint molecules (TIGIT, PD-1, CTLA-4, TIM-3, PD-L1), and immune cell proliferation (Ki67) as well as panCK as an epithelial cell marker for tumor detection. Comparison with clinical data revealed significant associations between a high fraction of intratumoral CD3+ T-cells (p=0.0182), cytotoxic T-cells (p=0.0192) and dendritic cells (p=0.0080) and favorable prognosis, and between a low fraction of intratumoral CD3+T-cells (p=0.0007) and advanced tumor stage. A high Ki-67 labelling index was linked to poor prognosis (p=0.0002) and nodal positivity in all 798 lung cancer patients (p<0.0001), as well as in the subsets of 441 lung adenocarcinomas (p=0.0002) and 219 lung squamous cell carcinomas (p=0.0015). No prognostic relevance was found for the expression of the immune checkpoint molecules TIGIT, PD-L1, TIM-3, CTLA-4 and PD-1 on the immune cells in our series of cancers. In conclusion, a high T-cell infiltrate is linked to beneficial tumor characteristics in non-small cell lung cancers. Citation Format: Lisa Hornsteiner, Natalia Gorbokon, Jonas B Raedler, Claudia Hube-Magg, Monika Kaszubowski, Nina Schraps, Katharina Möller, Florian Viehweger, Florian Lutz, Till S Clauditz, Christoph Fraune, Eike Burandt, Ronald Simon, Guido Sauter, Martin Reck, Klaus Raabe, Maximilian Lennartz, Stefan Steurer, Elena Bady. Prognostic impact of the immune environment in non-small cell lung cancer [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 6486.