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IL-33 provision by reprogrammed tumor fibroblastic stromal cells promotes local T cell activity and facilitates melanoma eradication

ABSTRACT: The tumor microenvironment (TME) is a complex mixture of tumor cells, immune cells, endothelial cells and fibroblastic stroma cells (FSC). While cancer-associated fibroblasts are generally seen as a tumor-promoting entity, it is conceivable that distinct FSC populations within the TME contribute to immune-mediated tumor control. Here, we show that intra-tumoral injection of a recombinant LCMV-based vaccine vector (r3LCMV) expressing the melanocyte differentiation antigen TRP2 results in T cell-dependent eradication of melanomas. Analysis of the TME revealed that viral vector transduction precipitates activation of particular FSC subsets. Using single-cell RNA-seq analysis, we identified a Cxcl13-expressing FSC population with a pronounced immune-stimulatory signature and increased expression of the inflammatory cytokine IL-33. Genetic ablation of Il33 in Cxcl13-Cre+ FSC impeded functionality of intratumoral T cells and consequently tumor control. Thus, reprogramming of distinct FSC subsets in the TME through LCMV-based vectors efficiently promotes tumor eradication by locally sustaining the activity of tumor-specific T cells.

INSTRUMENT(S): Illumina NovaSeq 6000

ORGANISM(S): Mus musculus

SUBMITTER: Mechthild Lütge

PROVIDER: E-MTAB-9407 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Fibroblastic reticular cells serve as primary immune checkpoint in visceral adipose tissues and secure peritoneal immunity

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2018-06-12 | E-MTAB-6886 | biostudies-arrayexpress

Fibroblastic reticular cells in the spleen - total splenic Stroma cells - single cell RNAseq dataset 2

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2019-03-27 | E-MTAB-7703 | biostudies-arrayexpress

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