Single cell RNAseq of immune and stromal cells in murine lung cancer
Immune responses against tumor cells depend on T lymphocyte attraction and activity within the tumor microenvironment. Specialized immune-interacting fibroblasts, commonly referred to as fibroblastic reticular cells (FRC), form specialized niches in secondary lymphoid organs, originate from embryonic progenitors and foster T cell activation. FRCs have also been detected in tertiary lymphoid structures (TLS) in tumors, differentiating from cancer associated fibroblasts. However, the identity and differentiation of niche-forming cells that foster intra-tumoral T cell activity have remained elusive. Here, we employed single cell RNA-sequencing of EYFP+ fibroblasts and GP33/34-Tetramer+CD8+ T cells from experimental murine lung cancer and cell fate-mapping analysis, which revealed the ability of FRC subsets in lung tumors to differentiate from progenitors situated in mural and adventitial sites. Ablation of FRC progenitors in Tumor T cell environments (TTEs) of murine lungs led to reduced anti-tumor T cell activity and loss of tumor control during experimental coronavirus vector-based immunotherapy. Collectively, our study defines lung cancer-associated FRC niches and key processes involved in stromal-T cell interaction that could pave the way for improved cancer immunotherapy.