UCSD researchers link overlooked molecule to better cancer immunotherapy

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SAN DIEGO — A study published Thursday by UC San Diego researchers found that targeting an overlooked immune cell and its molecular binding partner could improve cancer immunotherapy techniques.

Immunotherapy is a cancer treatment intended to enhance a patient’s immune system to give it a better chance of fighting cancer cells. Researchers and oncologists generally focus on a specific type of immune cell, known as CD8+ T cells, and a molecule the cell binds with to destroy cancer cells, called MHC-I.

UC San Diego researchers found that CD4+ T cells and a similar molecular binding partner known as MHC-II could be more effective that previous efforts with CD8+ T cells.

“The more we know about the ability of a person’s immune system to clear cancer cells before they take hold, and the more we can combine that with other information about their inherited risk factors or environmental exposures, the better we may get at predicting a person’s cancer susceptibility,” said Dr. Hannah Carter, the study’s senior author.

When antigen-fighting cells in the body detect an infected cell, they kill it before the cell can infect others around it. A previous study by Carter and first author Rachel Marty showed that people are more likely to get cancer early in life if their MHC-I molecule fails to destroy cancer-infected cells. As MHC-I destroys fewer cells, that likelihood goes up.

In the new study, Carter and her team found that the same was not true for MHC-II and that correlation similar to that of MHC-I couldn’t be detected.

“Imagine there are 100 mutated antigens that can cause cancer,” Carter said. “If a person’s MHC-I can only present 20 of those antigens, they would have less coverage than someone who can present 80. When people can’t present a lot of mutations, they tend to get cancer at an earlier age. That’s true for MHC-I, but we couldn’t find that same correlation for MHC-II, at least not in this early analysis.”

Researchers hope the discovery can translate into more accurate immunotherapy techniques by utilizing data from both MHC-I and MHC-II to determine how a patient will react to treatment.

“This may represent a step forward in our ability to select the best form of immunotherapy for individual patients and likewise help better predict response to immunotherapy,” co-author Dr. Maurizio Zanetti said. “I see this work as a major step to bridge cancer genomics and cancer immunity.”

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