Analysis of clonal expansion and crosstalk in the adaptive immune system in non-small cell lung cancer 3495

Abstract Description Objectives The adaptive immune system plays a critical role in the anti-tumor response. Understanding the crosstalk between these immune cell subsets could uncover novel therapeutic opportunities in non-small cell lung cancer (NSCLC). Methods Single-cell RNA sequencing (scRNA-seq) and immune repertoire sequencing were applied to CD4+ T cells, CD8+ T cells, and B cells isolated from tumor and matched normal tissues of three NSCLC patients. Findings were validated using publicly available datasets. Results Naïve CD4+ T cells were the predominant cell type across samples, while effector memory and cycling T cells exhibited the most significant clonal expansion. Clonally expanded T and B cell populations were detected in tumor samples from all patients. Antibody-secreting cells showed the highest clonal overlap with atypical memory B cells, suggesting an extrafollicular differentiation pathway. Ligand-receptor analysis identified the CCL5-CCR1 signaling axis as a potential interaction pathway between atypical memory B cells and clonally expanded effector memory T cells. Conclusion The integration of scRNA-seq and immune repertoire analysis provides a powerful tool to study the adaptive immune response in NSCLC. The CCL5-CCR1 axis may represent a novel mechanism linking T and B cell interactions in the tumor microenvironment, warranting further exploration for therapeutic targeting. Funding Sources Supported by the Austrian Research Promotion Agency (FFG). Topic Categories Tumor Immunology: Cellular Responses and Tumor Microevironment (TIME)