Telmisartan alters the transcriptomes of cancer associated fibroblasts and fibrocytes in a solid tumour model

Abstract

Cancer associated fibroblasts (CAFs) are the main contributors to fibrosis in solid tumours. Fibrosis can lead to increased tumoural stiffness, immune cell exclusion, and poor response to cancer therapies. However, therapeutically depleting CAFs has been shown to increase tumour progression and metastasis in some pre-clinical tumour models. Targeted approaches to inhibit CAF activity and decrease fibrosis without abrogating CAFs altogether may improve the effect of existing cancer therapies. We have previously shown that the blood pressure medication telmisartan decreases tumoural collagen, resulting in improved vascular perfusion, decreased hypoxia, and improved radiation treatment efficacy. To understand how telmisartan influences CAF populations in solid tumours, we conducted single cell RNA sequencing analyses of host cells isolated from tumours in mice treated with telmisartan. Telmisartan modified the transcriptomes of CAF populations, promoting the expression of chemokine signaling while decreasing the expression of extracellular matrix components in myCAFs. Telmisartan decreased expression of collagen transcripts in myCAFs and fibrocytes, indicating that telmisartan does not remove myCAFs but changes the myCAF transcriptome to become less fibrillar. Our work provides further support for using telmisartan to manipulate CAF populations in the solid tumour microenvironment to decrease collagen deposition and render tumours more responsive to current cancer therapies.

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BibTeX RIS

BibTeX

@misc{lee2026telmisartan,
  title = {{Telmisartan alters the transcriptomes of cancer associated fibroblasts and fibrocytes in a solid tumour model}},
  author = {C.-M. Lee and N. Telkar and B. J. Wadsworth and R. A. Cederberg and R. Shi and L. Zhan and P. Sekhon and M. Clark and M. G. Hall and K. N. Thomas and W. Lam and K. Bennewith},
  howpublished = {bioRxiv},
  year = {2026},
  month = sep,
  doi = {10.64898/2026.09.12.751091},
  url = {https://www.biorxiv.org/content/10.64898/2026.09.12.751091v1},
  note = {CC BY-NC-ND},
}

RIS

TY  - UNPB
TI  - Telmisartan alters the transcriptomes of cancer associated fibroblasts and fibrocytes in a solid tumour model
AU  - C.-M. Lee
AU  - N. Telkar
AU  - B. J. Wadsworth
AU  - R. A. Cederberg
AU  - R. Shi
AU  - L. Zhan
AU  - P. Sekhon
AU  - M. Clark
AU  - M. G. Hall
AU  - K. N. Thomas
AU  - W. Lam
AU  - K. Bennewith
PY  - 2026
DA  - 2026/09/12
PB  - bioRxiv
DO  - 10.64898/2026.09.12.751091
UR  - https://www.biorxiv.org/content/10.64898/2026.09.12.751091v1
AB  - Cancer associated fibroblasts (CAFs) are the main contributors to fibrosis in solid tumours. Fibrosis can lead to increased tumoural stiffness, immune cell exclusion, and poor response to cancer therapies. However, therapeutically depleting CAFs has been shown to increase tumour progression and metastasis in some pre-clinical tumour models. Targeted approaches to inhibit CAF activity and decrease fibrosis without abrogating CAFs altogether may improve the effect of existing cancer therapies. We have previously shown that the blood pressure medication telmisartan decreases tumoural collagen, resulting in improved vascular perfusion, decreased hypoxia, and improved radiation treatment efficacy. To understand how telmisartan influences CAF populations in solid tumours, we conducted single cell RNA sequencing analyses of host cells isolated from tumours in mice treated with telmisartan. Telmisartan modified the transcriptomes of CAF populations, promoting the expression of chemokine signaling while decreasing the expression of extracellular matrix components in myCAFs. Telmisartan decreased expression of collagen transcripts in myCAFs and fibrocytes, indicating that telmisartan does not remove myCAFs but changes the myCAF transcriptome to become less fibrillar. Our work provides further support for using telmisartan to manipulate CAF populations in the solid tumour microenvironment to decrease collagen deposition and render tumours more responsive to current cancer therapies.
ER  -

Abstract

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