Cancer-fighting protein depletes tumors and boosts the body’s immune system.

New cancer therapies can both deplete tumors and boost the body’s immune response against them.. (CREDIT: Creative Commons)

Tumor cells usually change their energy metabolism and increase glucose uptake, which promotes their rapid division and spread. This limits the availability of glucose to immune cells and therefore weakens the body’s anti-cancer immune response.

In search of proteins that simultaneously regulate cancer cell metabolism and act on immune cells in tumors, a team of researchers at the Massachusetts General Hospital (MGH) recently identified a potential target for a therapy that can both deplete tumors and enhance the immune response. against them.

For the study, which is published in the journal Cancer Discovery, Keith T. Flaherty, MD, director of clinical research at MGH Cancer Center and professor of medicine at Harvard Medical School, and colleagues have developed a new computational tool called BipotentR that can identify targets which block immune activation as well as stimulate a second user-defined pathway (in this case, metabolism).

Applied to gene expression data in cancer patients treated with immunotherapy, as well as in cell lines and animal models, the tool identified 38 cancer cell-specific immuno-metabolic regulators.

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Artificial intelligence methods showed that the level of activity of these regulators in tumors predicted the results of treatment of patients after immunotherapy.

The topmost regulator identified, ESRRA (estrogen-related receptor alpha), is upregulated in immunotherapy-resistant tumors of many types. Inhibition of ESRAA killed tumors by suppressing energy metabolism and activating two immune mechanisms involving different types of immune cells.

ESRRA inhibition was safe when tested in mice, and its effect on energy metabolism was focused on cancer cells.

Description and validation of the BipotentR immune module. (CREDIT: Cancer discovery)

The scientists also demonstrated that BipotentR can be applied to other survival mechanisms used by cancer cells, such as their ability to stimulate the formation of blood vessels to increase their blood supply.

Thus, BipotentR, available at http://www.bipotentr.com, provides a resource for discovering individual drugs that can act through a single cancer-related pathway while stimulating an immune response.

Inhibition of ESRRA induces antitumor immunity in vivo. (CREDIT: Cancer discovery)

“These results provide a simple biomarker to predict response/non-response to immunotherapy and support ERRA as a therapeutic target,” says Flaherty.

Key Findings

• By developing a new computational tool, the researchers identified a potential target for cancer therapy that could both deplete tumors and boost the body’s immune response against them.

• A target called estrogen-coupled receptor alpha may also be a marker for predicting which patient will benefit from immunotherapy.

Additional MGH collaborators include Philip Munson, Dejan Eurek, and David E. Fisher.

This work was supported by the Adelson Medical Research Foundation.

For more science news, visit our New Innovations section at The bright side of the news.

Note. Materials provided above by Massachusetts General Hospital. Content can be edited for style and length.

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