A new study led by researchers at The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC - James) reveals how a clotting protein and blood platelets can promote cancer progression and suppress immune responses to cancer.
The findings show how thrombin, a clotting protein in the blood, causes blood platelets to release transforming growth factor-beta 1 (TGF-b1), which is known for promoting disease progression in breast, prostate, colorectal and other cancers, and for suppressing immune-system responses to cancer.
Additionally, TGF-b1 is a leading cause for the failure of immune therapies such as PD1 inhibitors in cancer patients. This study may offers a new explanation for what causes tumors to resist immune therapies and become sensitive to the therapeutic agents.
The researchers used animal models to show that inhibiting thrombin activity prevents the release of TGF-1b and makes tumors that were resistant to anti-PD-1 immunotherapy susceptible to these agents.
The findings are reported in the journal Science Translational Medicine .
"In this study, we describe a direct connection between thrombin and TGF-b1, a cytokine that promotes tumor progression and suppresses the ability of immune cells to attack the tumor," says principal investigator Zihai Li, MD, PhD, a professor in the Division of Medical Oncology at Ohio State and the founding director of the Pelotonia Institute for Immuno-Oncology (PIIO) at the OSUCCC - James. Li also holds the Klotz Memorial Chair in Cancer Research at The Ohio State University College of Medicine
"We also show that systemically interfering with this mechanism prevents the release of TGF-1b and leads to changes in the tumor microenvironment that are favorable to anticancer immune responses," says Li, who is a member of the OSUCCC - James Translational Therapeutics Program.
Li notes that cancer is similar to an unhealed wound that constantly activates the coagulation pathway and generates high concentrations of thrombin in and around a tumor. That, in turn, causes chronic platelet activation and release of TGF-1b.
TGF plays important roles in cancer development. Specifically, TGF-b1 alters the tumor microenvironment in ways that protect cancer cells from attack by immune cells." Zihai Li, principal investigator
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