Researchers at the University of Pittsburgh and UPMC Hillman Cancer Center have identified a method to rejuvenate exhausted T cells by blocking the absorption of lactate, a metabolic byproduct produced by cancer cells. This breakthrough was published in Nature Immunology.
The study highlights that when T cells are continuously exposed to tumors, they become less effective due to the expression of co-inhibitory receptors. The team discovered that a solute carrier protein, MCT11, which imports lactate, was significantly elevated in terminally exhausted T cells. By inhibiting MCT11, the T cells displayed improved functionality and tumor control in mouse models of melanoma, colorectal carcinoma, and head and neck cancer.
Furthermore, the research demonstrated that combining the MCT11 antibody with existing therapies, such as anti-PD1, enhanced tumor elimination in mice. The findings suggest that targeting MCT11 could offer a new therapeutic approach with potentially fewer side effects compared to traditional immunotherapies.
The authors are now working on optimizing the MCT11 antibody for human T cells, aiming for future clinical trials. This research opens avenues for exploring how immune cells interact with their metabolic environment to improve cancer treatment outcomes.