New immunotherapeutic approach reverses T-cell depletion

Researchers have discovered an approach to reduce T-cell depletion in immunotherapy-resistant tumors, according to a study published in . cell report. Blocking the activity of the protein P-selectin glycoprotein ligand 1 (PSGL-1), which promotes T cell exhaustion, can slow T cell exhaustion and restore cells to normal function.

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“Slowing or reversing T-cell exhaustion is a major focus in cancer research, and many researchers are working on different ways to achieve this,” said lead author Jennifer Hope, Ph.D. Drexel University) said in a press release.

Cancer and chronic diseases cause ongoing stress on the cells of the immune system. As a result, her T cells of the immune system stop functioning and become “exhausted.” Without active T cells, the body cannot fight cancer or kill tumor cells. Therefore, the overarching goal of immunotherapy research is to deplete reverse T cells, support immune function, and fight cancer.

PSGL-1 is a protein found in most blood cells. Researchers first found that PSGL-1 promotes T-cell depletion when studying PSGL-1-deficient mice. Their latest study used an antibody that actively targets and blocks PSGL-1 activity in mice with immunotherapy-resistant melanoma. The treatment not only slowed fatigue, but also converted exhausted T cells to functioning T cells, significantly reducing tumor growth.

The treatment is very unique from other immunotherapies because it restores T-cell function, Hope said in a press release. It also differs in that it targets multiple aspects of the T cell depletion process.

Cancers can be resistant to treatment with only one type of therapy, said lead author Linda Bradley, Ph.D., professor of cancer metabolism and microenvironment at Sanford Burnham Prebys. said in a press release. So while it could be an effective treatment on its own, it also “has great potential to work synergistically with existing treatments,” Burnham said. Therefore, it may be a particularly beneficial treatment for patients with immunotherapy-resistant cancer.

Recognizing that PSGL-1-blocking antibodies have therapeutic potential against various types of cancer, the research team also studied them in mesothelioma mice. Although the use of antibodies or recombinant proteins as immunotherapy in humans is not clinically approved, this study may herald new immunotherapeutic approaches that are effective against treatment-resistant types of cancer. .

“The more tools we have to slow or reverse T-cell exhaustion in different ways, the better precision medicine we have and the potential for more cancer patients to benefit from immunotherapy. ,” Bradley said in a press release.

reference

Sanford Burnham Presby. Revive her exhausted T cells to fight immunotherapy-resistant cancer. news release. May 3, 2023. Accessed May 5, 2023. https://www.eurekalert.org/news-releases/988211

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