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"In this study, we were able to show that the function of these channels in T-cells from cancer patients is decreased which results in a decreased T-cell accumulation in solid tumors," Conforti says.
These types of channels require a signaling molecule called calmodulin to bind to them in order to function to their full capacity; this is needed even more in cancer T-cells.
Using several intricate microscopy imaging techniques on T-cells isolated from the blood of cancer patients, the team found out that, as compared to T-cells from healthy individuals, the cancer T-cells have fewer calmodulin molecules in their membranes.
"This would mean that there is less calmodulin binding to the channels in the T-cells from cancer patients," Conforti says. "As previously stated, the channels do not function if the calmodulin does not bind to them. Thus, the decreased calmodulin binding in T-cells from cancer patients results in decreased function and leads to reduced tumor infiltration and killing of the cancer cells."
"So back to our soldiers: If they were present at a battlefield, but none of them have any weaponry, this will hinder their ability to infiltrate the enemy lines. Now, if we arm each soldier adequately, we would boost their function. They can do their job. Similarly, we observed that if we increase the function of these channels by drugs that enhance their activity, the cancer patients' T-cells can penetrate the tumors better and also produce increased cytokines which can kill tumor cells," Chimote says. "These are exciting findings that could lead to additional treatments for patients with cancer."
"These findings strengthen the therapeutic potentials of [these] activators, which could restore cytotoxic T-cell functionality and can ultimately lead to additional immunotherapeutic options for patients with cancer," Conforti adds. Source:
University of Cincinnati Journal reference:
Chimote, A.A., et al. (2020) A Compartmentalized Reduction in Membrane-Proximal Calmodulin Reduces the Immune Surveillance Capabilities of CD8+ T Cells in Head and Neck Cancer. Frontiers in Pharmacology . doi.org/10.3389/fphar.2020.00143 .
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