Overview

• Researchers report that cancer cells degrade myelin around nerves, causing injury that triggers a regenerative inflammatory program that becomes chronic.
• The chronic nerve-injury signaling fosters immune exhaustion and an immunosuppressive tumor microenvironment associated with resistance to anti-PD-1 therapy.
• Analyses of clinical trial samples using genetic, bioinformatic, and spatial profiling linked perineural invasion to reduced neuronal health rather than a general cancer effect.
• Targeting nodes within the cancer-induced nerve injury pathway reversed resistance and improved responses to anti-PD-1 therapy in preclinical models.
• The work, published in Nature, was a collaboration among MD Anderson, Brigham and Women's Hospital, the University of Michigan, Moffitt Cancer Center, and Queen's University, supported in part by the James P. Allison Institute and MD Anderson's Cancer Neuroscience Program.