Cancer's immune escape trick may backfire: shutting down MHC class I exposes tumors to helper T cells
Researchers at Baylor College of Medicine, with the University of Michigan, report in Nature Immunology that when tumors switch off MHC class I to evade killer T cells, they become more vulnerable to helper T cells, which trigger iron-driven cell death. The same pattern appeared in graft-versus-host disease and in checkpoint-inhibitor patient data.
A Baylor College of Medicine team, working with the University of Michigan Rogel Cancer Center, reports in Nature Immunology that the long-held divide between MHC class I (killer T cells) and MHC class II (helper T cells) is more complex than thought. Many tumors switch off MHC class I to hide from CD8+ killer T cells. In mouse models and human samples, lowering MHC class I instead made cancer cells more vulnerable to CD4+ helper T cells, which drove ferroptosis, an iron-dependent form of cell death. The effect also showed up in graft-versus-host disease after bone marrow transplants and correlated with outcomes in checkpoint-inhibitor patients.