A team led by Dr. Pavan Reddy, director of the Dan L Duncan Comprehensive Cancer Center at Baylor College of Medicine, announced on Mar. 24 a discovery that reveals a new way T-cells in the immune system attack target cells. The findings challenge established ideas in immunology and could impact cancer treatment and bone marrow transplantation.
The research is significant because it shows that CD4+ T cells can kill cancer cells when those cells lose MHC I expression—a common tactic used by tumors to avoid detection by CD8+ T cells. This expands understanding of how the body’s immune defenses work and may lead to more effective immunotherapies.
The study was conducted in collaboration with Drs. Arul Chinnaiyan and Marcin Cieslik from University of Michigan Rogel Cancer Center, along with graduate students from both institutions. Using advanced studies in mice models and human samples, researchers found that without MHC I expression, cancer cells become more vulnerable to ferroptosis—a type of cell death driven by iron and oxidative stress—triggered by CD4+ T cells. The effect was also observed in models of graft-versus-host disease after bone marrow transplant.
Chinnaiyan’s team analyzed large datasets from patients who received checkpoint blocker therapy for solid tumor cancers, finding clinical correlations for these observations. "Our work, if further validated, will have implications for T cell-mediated immune responses beyond cancer and transplant immunology," Reddy said. "This may allow for the development of novel strategies that target MHC class I and CD4+ T cells to leverage the beneficial side of immunity or mitigate unwanted immune responses." Other contributors included Emma Lauder, Mahnoor Gondal, Meng-Chih Wu, Akira Yamamoto, Laure Maneix, Dongchang Zhao and Yaping Sun.
Baylor College of Medicine focuses on advancing research, education, patient care, and community service as an independent health sciences university according to the official website. It provides education across its schools while engaging in clinical partnerships according to the official website. Paul Klotman holds the roles of president, chief executive officer, and executive dean at Baylor College of Medicine according to the official website.
Baylor College of Medicine contributes to community service as one of its core missions according to the official website, collaborates in environments promoting integrated health sciences according to the official website, and advances biomedical research through partnerships according to the official website.
