Ring, Sandra S; Cupovic, Jovana; Onder, Lucas; Lütge, Mechthild; Perez-Shibayama, Christian; Gil-Cruz, Cristina; Scandella, Elke; De Martin, Angelina; Mörbe, Urs; Hartmann, Fabienne; Wenger, Robert; Spiegl, Matthias; Besse, Andrej; Bonilla, Weldy V; Stemeseder, Felix; Schmidt, Sarah; Orlinger, Klaus K; Krebs, Philippe; Ludewig, Burkhard and Flatz, Lukas (2021). Viral vector-mediated reprogramming of the fibroblastic tumor stroma sustains curative melanoma treatment. Nature communications, 12(1), p. 4734. Nature Publishing Group 10.1038/s41467-021-25057-w
|
Text
s41467-021-25057-w.pdf - Published Version Available under License Creative Commons: Attribution (CC-BY). Download (3MB) | Preview |
The tumor microenvironment (TME) is a complex amalgam of tumor cells, immune cells, endothelial cells and fibroblastic stromal cells (FSC). Cancer-associated fibroblasts are generally seen as tumor-promoting entity. However, it is conceivable that particular FSC populations within the TME contribute to immune-mediated tumor control. Here, we show that intratumoral treatment of mice with a recombinant lymphocytic choriomeningitis virus-based vaccine vector expressing a melanocyte differentiation antigen resulted in T cell-dependent long-term control of melanomas. Using single-cell RNA-seq analysis, we demonstrate that viral vector-mediated transduction reprogrammed and activated a Cxcl13-expressing FSC subset that show a pronounced immunostimulatory signature and increased expression of the inflammatory cytokine IL-33. Ablation of Il33 gene expression in Cxcl13-Cre-positive FSCs reduces the functionality of intratumoral T cells and unleashes tumor growth. Thus, reprogramming of FSCs by a self-antigen-expressing viral vector in the TME is critical for curative melanoma treatment by locally sustaining the activity of tumor-specific T cells.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
04 Faculty of Medicine > Service Sector > Institute of Pathology > Immunopathology |
UniBE Contributor: |
Krebs, Philippe |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
2041-1723 |
Publisher: |
Nature Publishing Group |
Language: |
English |
Submitter: |
Philippe Krebs |
Date Deposited: |
27 Aug 2021 08:56 |
Last Modified: |
05 Dec 2022 15:52 |
Publisher DOI: |
10.1038/s41467-021-25057-w |
PubMed ID: |
34354077 |
BORIS DOI: |
10.48350/157989 |
URI: |
https://boris.unibe.ch/id/eprint/157989 |
Actions (login required)
 |
Edit item |