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.
Researchers at the University of Michigan Rogel Cancer Center have discovered a key reason why some cancers do not respond to immunotherapy : A metabolite transporter within the tumor microenvironment that blocks a key type of tumor cell death integral to immune response. Tumor cells adapt their metabolic mechanisms to evade immune-base therapies. Understanding how these mechanisms of immune resistance work can provide new targets to refine immune-based treatments so they benefit more patients.
Our discovery is one step in that direction." 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 identified SLC13A3 as a transporter of the metabolite itaconate in tumor cells that causes the cell to be resistant to ferroptosis, a form of regulated cell death.
Zou and colleagues were first to report that immune-regulated ferroptosis occurs in tumor cells and plays a key role in cancer immunotherapy, in two previous papers. In the new study, published in Cancer Cell , researchers found that high levels of SLC13A3 in patient tumor samples was associated with poor response to immunotherapy and poor overall survival in patients. They tested this in tumor sample.
