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Citations to this article

Pericyte phenotype switching alleviates immunosuppression and sensitizes vascularized tumors to immunotherapy in preclinical models
Zhi-Jie Li, … , Gabriel Y.F. Lee, Ruth Ganss
Zhi-Jie Li, … , Gabriel Y.F. Lee, Ruth Ganss
Published September 17, 2024
Citation Information: J Clin Invest. 2024;134(18):e179860. https://doi.org/10.1172/JCI179860.
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Research Article Oncology Article has an altmetric score of 12

Pericyte phenotype switching alleviates immunosuppression and sensitizes vascularized tumors to immunotherapy in preclinical models

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Abstract

T cell–based immunotherapies are a promising therapeutic approach for multiple malignancies, but their efficacy is limited by tumor hypoxia arising from dysfunctional blood vessels. Here, we report that cell-intrinsic properties of a single vascular component, namely the pericyte, contribute to the control of tumor oxygenation, macrophage polarization, vessel inflammation, and T cell infiltration. Switching pericyte phenotype from a synthetic to a differentiated state reverses immune suppression and sensitizes tumors to adoptive T cell therapy, leading to regression of melanoma in mice. In melanoma patients, improved survival is correlated with enhanced pericyte maturity. Importantly, pericyte plasticity is regulated by signaling pathways converging on Rho kinase activity, with pericyte maturity being inducible by selective low-dose therapeutics that suppress pericyte MEK, AKT, or notch signaling. We also show that low-dose targeted anticancer therapy can durably change the tumor microenvironment without inducing adaptive resistance, creating a highly translatable pathway for redosing anticancer targeted therapies in combination with immunotherapy to improve outcome.

Authors

Zhi-Jie Li, Bo He, Alice Domenichini, Jiulia Satiaputra, Kira H. Wood, Devina D. Lakhiani, Abate A. Bashaw, Lisa M. Nilsson, Ji Li, Edward R. Bastow, Anna Johansson-Percival, Elena Denisenko, Alistair R.R. Forrest, Suraj Sakaram, Rafael Carretero, Günter J. Hämmerling, Jonas A. Nilsson, Gabriel Y.F. Lee, Ruth Ganss

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Total citations by year

Year: 2025 2024 Total
Citations: 4 1 5
Citation information
This citation data is accumulated from CrossRef, which receives citation information from participating publishers, including this journal. Not all publishers participate in CrossRef, so this information is not comprehensive. Additionally, data may not reflect the most current citations to this article, and the data may differ from citation information available from other sources (for example, Google Scholar, Web of Science, and Scopus).

Citations to this article (5)

Title and authors Publication Year
Glucose-dependent insulinotropic polypeptide receptor signaling modulates gut inflammation in mice
Rola Hammoud, Kiran Kaur, Jacqueline Koehler, Laurie Baggio, Chi Wong, Katie Advani, Bernardo Yusta, Irina Efimova, Fiona Gribble, Frank Reimann, Sigal Fishman, Chen Varol, Daniel Drucker
JCI Insight 2025
Selective tubulin-binding drugs induce pericyte phenotype switching and anti-cancer immunity.
He B, Wood KH, Li ZJ, Ermer JA, Li J, Bastow ER, Sakaram S, Darcy PK, Spalding LJ, Redfern CT, Canes J, Oliveira M, Prat A, Cortes J, Thompson EW, Littlefield BA, Redfern A, Ganss R, He B, Wood KH, Li ZJ, Ermer JA, Li J, Bastow ER, Sakaram S, Darcy PK, Spalding LJ, Redfern CT, Canes J, Oliveira M, Prat A, Cortes J, Thompson EW, Littlefield BA, Redfern A, Ganss R
EMBO molecular medicine 2025
Pericytes in castration-resistant prostate cancer associated with disease progression and immunotherapy response: insights from single-cell analysis
Qiu Y, Wang Y, Liu J, Sun K, Horie S, Bing Z, Hou Q
Cancer Cell International 2025
Deficiency of Fibroblast Growth Factor 2 Promotes Contractile Phenotype of Pericytes in Ascending Thoracic Aortic Aneurysm
Huang W, Hill JC, Patel S, Richards TD, Sultan I, Kaczorowski DJ, Phillippi JA
American journal of physiology. Heart and circulatory physiology 2025
Pericytes in Glioblastoma: Hidden Regulators of Tumor Vasculature and Therapy Resistance
Salazar-Saura I, Pinilla-Sala M, Megías J, Navarro L, Roselló-Sastre E, San-Miguel T
Cancers 2024

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Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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