New work from the Fecci Lab may explain why immunotherapies fail in the treatment of brain tumors.
“One of the key reasons that immunotherapies fail in brain tumors and other cancers is that the T cells needed for effectiveness become ‘exhausted’ over time,” Peter Fecci, MD, PhD, the paper’s senior author said. “This manuscript serves to uncover some of the mechanisms by which T cell exhaustion arises in tumors. Interestingly, we find that it’s not the tumor itself, but the infiltrating macrophages that appear responsible.”
In “Antigen presentation by tumor-associated macrophages drives T cells from a progenitor exhaustion state to terminal exhaustion,” published by Immunity on Dec. 25, 2024, Fecci’s team defined a relevant parameter – the intratumoral progenitor exhaustion-to-terminal exhaustion ratio (PETER) - which decreased with tumor progression in solid cancers.
“When PETER can be increased through the removal of macrophages, immunotherapies begin to work,” Fecci said.