Elucidate how dendritic cells affect T cells' function in the TME of non-small cell lung cancer

Division Of Basic Sciences - Nci

Investigators

Abstract

Following the development of our two-photon imaging platform and the uLIPSTIC system to visualize and trace interactions between tumor-specific CD8 T cells and type 1 conventional dendritic cells (cDC1) in the NSCLC tumor microenvironment (TME), we have expanded our investigation using single-cell RNA sequencing (scRNA-seq). Our transcriptomic analyses confirmed that the majority of CD8 T cells interacting with cDC1 exhibit a stem-like phenotype, reinforcing the hypothesis that cDC1 support the maintenance and function of stem-like CD8 T cells within tumors. Notably, we also identified a distinct population of Tc17 cells engaging with cDC1, suggesting a broader and more complex spectrum of cDC1-T cell interactions than previously appreciated. To functionally dissect the molecular pathways underlying these interactions, we established an in vivo spatial CRISPR screening platform based on the PerturbView system. This high-throughput approach enables the spatially resolved interrogation of gene function within the TME, offering unprecedented insight into the molecular circuits governing dendritic cell-T cell communication. Collectively, these advancements position us to uncover key regulatory nodes that may be leveraged to enhance T cell-mediated anti-tumor responses and improve immunotherapeutic strategies for NSCLC.