Researchers discover new vulnerable target in cancer cells

Volume 9, Issue 1, March 2020

Summary

An antibody developed at Mayo Clinic can make tumors more sensitive to radiotherapy and chemotherapy.

Photograph of Robert W. Mutter, M.D.

Robert W. Mutter, M.D.

Photograph of Zhenkun Lou, Ph.D.

Zhenkun Lou, Ph.D.

Photograph of Haidong Dong, M.D., Ph.D.

Haidong Dong, M.D., Ph.D.

The protein PD-L1 is frequently present on the surface of cancer cells and is known for its role in helping cancer cells escape the immune system by shutting down the anti-tumor function of immune cells. Now, a team of Mayo Clinic-led researchers has discovered a new role for PD-L1 — finding that cancer cells also use PD-L1 to promote their resistance to treatment by improving their ability to fix DNA damage caused by radiotherapy or chemotherapy.

But Robert W. Mutter, M.D., Zhenkun Lou, Ph.D., and Haidong Dong, M.D., Ph.D., said an antibody called H1A can be used to target this function of PD-L1 in cancer. Dr. Mutter is a radiation oncologist and Drs. Lou and Dong are researchers, all at Mayo Clinic in Rochester, Minnesota.

H1A was developed by Dr. Dong with Xinyi Tu, Ph.D., a postdoctoral fellow at Mayo Clinic in Rochester, Minnesota. The pair discovered that H1A decreases the levels of PD-L1 inside cancer cells, making tumors more sensitive to radiotherapy and chemotherapy.

"Our findings suggest that PD-L1 inside of cancer cells is a new target to sensitize cancer to radiotherapy and chemotherapy," Dr. Mutter said. "In the future, the H1A or other strategies that prevent PD-L1 from carrying out this newly discovered role inside of cancer cells may be used to improve the efficacy of cancer therapy."

Dr. Dong is part of Mayo Clinic Cancer Center's David F. and Margaret T. Grohne Cancer Immunology and Immunotherapy Program. Researchers with the program study the mechanisms involved in cancer development and how the immune system responds to cancer, and also develop and test immune therapies for cancer patients.

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