GSE131957
Identification of a DC1 immuno-regulatory module that limits antitumor CD8+ T cell immunity in lung cancer lesions.
While conventional dendritic cells (DC)1 and DC2 are found in tumors, DC1 were shown to control tumor response to checkpoint blockade in preclinical models and are associated with better overall survival in cancer patients, reflecting their specialized ability to prime CD8+ T cell responses. Paradoxically, DC1 can also be found in tumors that resist checkpoint blockade, suggesting that, like many tumor infiltrating T cells, DC1 functionality may be altered in tumors.  To address this question, we performed scRNAseq analyses to characterize DC gene architecture in mouse non-small cell lung cancer (NSCLC) lesions. To understand the relationship of the resulting transcriptional signatures with antigen uptake and migration, we profiled lung DCs in CCR7-/- mice, or DCs that had taken up (i) GFP from GFP-expressing tumors that had been seeded in the lung, and (ii) fluorescent microbeads that had been applied intranasally. Overall design: CITEseq of DCs from the lungs of wild-type tumor-naïve, tumor-bearing, or CCR7-/- mice. Bulk RNAseq of cDC1 sorted from the lungs of mice bearing GFP-expressing tumors based on GFP antigen uptake, or from the lungs of mice that were subjected to intranasal application of fluorescent microbeads and sorted based on bead uptake.