Abstract 5257: Functional profiling of γδ T cell subsets in malignant pleural effusion and their prognostic value in advanced lung cancer

Abstract The tumor immune microenvironment reflects a patient's immune reserve and offers valuable insights for clinical decision-making. It has the potential to stratify late-stage cancer patients, identifying those likely to benefit from aggressive therapies and those better suited for palliative care. However, obtaining detailed immune profiling from tumor tissues often requires invasive biopsies and poses additional risks. Malignant pleural effusion (MPE), a common complication in advanced lung cancer, provides a minimally invasive alternative for evaluating microenvironmental immune dynamics via thoracentesis. In this study, we analyzed the immune cell composition of malignant pleural effusions (MPE) from 73 patients with late-stage lung adenocarcinoma using high-dimensional spectral flow cytometry and a comprehensive panel of immunophenotypic and functional markers. Our analysis focused on cytotoxic immune cell populations, including NK cells, NKT cells, CD8+ T cells, and γδ T cells. Notably, γδ T cells constituted approximately 1.4% of viable cells, with the Vδ1 and Vδ2 subpopulations representing 32.3% and 46.6% of the γδ T cell compartment, respectively. Higher γδ T cell abundance was associated with shorter overall survival, while no correlation was observed for other immune cell populations. Further analysis revealed that a higher Vδ2/Vδ1 ratio correlated with poorer clinical outcomes. Conversely, elevated expression of the activating receptor DNAM-1 (CD226) on Vδ1 cells was observed in long-term survivors (>2 years) compared to short-term survivors (<6 months), independent of mutation type or treatment modality. These findings were validated using the TCGA lung cancer datasets, confirming a strong link between high DNAM-1 expression and extended survival. In conclusion, γδ T cell subpopulations in MPE, particularly the Vδ1 and Vδ2 subsets, are promising biomarkers for immune fitness and prognosis in advanced lung adenocarcinoma. These results highlight the potential of γδ T cells to identify late-stage patients likely to benefit from aggressive therapies and emphasize the need for larger-scale studies to confirm these findings. Citation Format: Tsai-Tsen Shih, Yi-Chieh Wu, Hsing-Chen Tsai. Functional profiling of γδ T cell subsets in malignant pleural effusion and their prognostic value in advanced 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 5257.