The immune system is a major target for cancer treatments. Immune checkpoint inhibitors and CAR-T cell therapy can dramatically improve outcomes for many cancers. But for about 70% of patients, these therapies don't work.
Michigan Medicine - University of MichiganNov 8 2024 The immune system is a major target for cancer treatments. Immune checkpoint inhibitors and CAR-T cell therapy can dramatically improve outcomes for many cancers. But for about 70% of patients, these therapies don't work.
Weiping Zou, M.D., Ph.D., senior study author, director of the Center of Excellence for Cancer Immunology and Immunotherapy at the Rogel Cancer Center Researchers then validated the findings in tumor bearing mouse models in which tumor SLC13A3 was knocked out. Deleting SLC13A3 led to reduced tumor development and progression, while restoring SLC13A3 caused tumor progression. They also noted increased immune cells in the mice in which tumor SLC13A3 was deleted, compared to those expressing SLC13A3.
In collaboration with Shaomeng Wang, M.D., Ph.D., and team, researchers created a structural model of SLC13A3 to screen and identify a potential inhibitor, SLC13A3i, that could prevent tumor cells from taking up itaconate and reverse ferroptosis resistance. They tested this inhibitor in mice as a single therapy and in combination with an immune checkpoint inhibitor. The SLC13A3 inhibitor alone reversed the ferroptosis resistance and treated cancers in mice.
Immune Response Immunotherapy Cell Cell Death Ferroptosis Immune System Immunity Medicine Metabolite Ph Research Tumor
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