ENAapplication/xmlftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR218/041/SRR21882941/SRR21882941.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR218/035/SRR21882935/SRR21882935.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR218/030/SRR21882930/SRR21882930.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR218/037/SRR21882937/SRR21882937.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR218/034/SRR21882934/SRR21882934.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR218/045/SRR21882945/SRR21882945.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR218/043/SRR21882943/SRR21882943.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR218/039/SRR21882939/SRR21882939.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR218/032/SRR21882932/SRR21882932.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR218/042/SRR21882942/SRR21882942.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR218/036/SRR21882936/SRR21882936.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR218/044/SRR21882944/SRR21882944.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR218/040/SRR21882940/SRR21882940.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR218/038/SRR21882938/SRR21882938.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR218/033/SRR21882933/SRR21882933.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR218/031/SRR21882931/SRR21882931.fastq.gzprimaryOK200GenomicsComputational and Systems Biology, Memorial Sloan Kettering Cancer Centerhttps://www.ebi.ac.uk/ena/browser/view/PRJNA889847Mus musculusxref:PubMed:37127830While regulatory T (Treg) cells are traditionally viewed as professional suppressors of antigen presenting and effector T cells in both autoimmunity and cancer, recent findings of distinct Treg functions in tissue maintenance suggest that their regulatory purview extends to a wider range of cells and is broader than previously assumed. To elucidate tumoral Treg “connectivity” to diverse tumor-supporting accessory cell types, we explored immediate early changes in their single cell transcriptomes upon punctual Treg depletion in experimental lung cancer and injury-induced inflammation. Prior to any notable T cell activation and inflammation, fibroblasts, endothelial and myeloid cells exhibited pronounced changes in their gene expression in both cancer and injury settings. Factor analysis revealed shared Treg-dependent gene programs, foremost, prominent upregulation of VEGF signaling-related genes upon Treg deprivation in either setting, as well as in Treg-poor vs Treg-rich human lung adenocarcinomas. Accordingly, punctual Treg depletion combined with short-term VEGF blockade showed markedly improved control of PD-1 blockade-resistant lung adenocarcinoma progression in mice compared to the corresponding monotherapies, highlighting a promising factor-based querying approach to elucidating novel rational combination treatments of solid organ cancers. Overall design: Lungs were collected from KrasLSL-G12D/WTTrp53fl/fl Foxp3GFP-DTR (KP-DTR) mice harboring ~3 months old Adenicarcinomas, following 48 hr treatment with Diphteria toxin (DT) to deplete Tregs, or PBS as control. Lungs were perofused and snap-frozen in OCT. All samples were sections with a Cryostat to a thickness of 10um.ENAfalseConserved transcriptional connectivity of regulatory T cells in the tumor microenvironment informs novel combination cancer therapy strategies [visium]Conserved transcriptional connectivity of regulatory T cells in the tumor microenvironment informs novel combination cancer therapy strategies [visium]2025-09-242023-05-05PRJNA889847GSE2153611009037127830