January 11, 2024

CPOD Faculty Publication Spotlight - Núñez Lab

Lo BC, Kryczek I, Yu J, Vatan L, Caruso R, Matsumoto M, Sato Y, Shaw MH, Inohara N, Xie Y, Lei YL, Zou W, Núñez G. Science. 2024 Jan 5;383(6678):62-70. Microbiota-dependent activation of CD4+ T cells induces CTLA-4 blockade-associated colitis via Fcγ receptors.


"Antibodies that target CTLA-4 can stimulate anti-cancer immunity but also cause off-target inflammatory pathologies in the gut.  We established a new mouse model of colitis that is triggered by CTLA-4 blockade, and determined that this inflammatory side effect is caused by the Fc domain of the anti-CTLA-4 antibodies which leads to the depletion of a subset of immune suppressive regulatory T cells in the gut.  Notably, we found that anti-CTLA-4 nanobodies which lack an Fc domain can effectively promote anti-cancer responses without causing colitis."
Pictured left to right: Dr. Bernard Lo, Ph.D. (Research Investigator, Pathology, University of Michigan) and Dr. Gabriel Núñez, M.D. (Professor, Pathology, University of Michigan)