As cancer cells grow, they pump out metabolic byproducts such as lactic acid into the tumor microenvironment. Exhausted T cells—which have lost their cancer-fighting oomph—consume this lactic acid, which further saps their energy, according to new research from the University of Pittsburgh and UPMC Hillman Cancer Center. When the researchers blocked the protein that imports lactic acid into cells, exhausted T cells gained a new lease on life, which led to improved tumor control in mouse models of cancer.
The findings are published in Nature Immunology . "Blocking access to inhibitory metabolites is a completely new take on how we can reinvigorate the immune system ," said senior author Greg Delgoffe, Ph.D.
professor of immunology at Pitt and director of the Tumor Microenvironment Center at UPMC Hillman. "We often think of exhausted T cells being useless, but this study shows that we can actually get juice out of these cells by blocking negative effects of the tumor microenvironment ." When continually exposed to tumors, T cells progressively become less effective due to expression of coinhibitory receptors that act like brakes.
Progenitor exhausted T cells, which still retain some cancer-killing function, can deteriorate further to a terminally exhausted state. Most immunotherapies, including the checkpoint inhibitor drugs anti-PD1 and anti-CTLA4, attempt to release these brakes by blocking coinhibitory receptors. "Checkpoint inhibitors, which are the main weapons in our .
