1221-NF2 Loss Mediates Resistance to Immunotherapy

This research identifies a critical genetic mechanism that causes mesothelioma to become resistant to CAR T cell and anti-PD-1 immunotherapies. Scientists discovered that the loss of the NF2 tumor suppressor gene triggers the activation of the Hippo pathway, which actively transforms the environment surrounding the tumor. This genetic deficiency recruits immunosuppressive myeloid cells—specifically macrophages—that shield the cancer from the immune system's attack. Importantly, this resistance is site-specific and can be reversed by pharmacologically targeting these myeloid cells or inhibiting the Hippo pathway. By combining these interventions with standard treatments, the study offers a new therapeutic strategy to restore the efficacy of immunotherapy in patients with relapsed disease. These findings emphasize that the success of modern cancer treatments depends on the dynamic interplay between a tumor's genetics and its local immune environment.References:Lopez-Lago M A, Taleb M, Ningoo M, et al. Loss of tumor suppressor NF2 mediates resistance to CAR T cell and anti-PD-1 therapy: Strategies to restore immunotherapy sensitivity[J]. Med, 2026.前往小宇宙评论区与主播互动