Nat Med: molecular mechanism of whether glioma responds to immunosuppressive checkpoint inhibitors

February 17, 2019 / bioin / - although immunocheckpoint inhibitors have been successfully used to treat a series of tumors, their efficacy in the treatment of gliomas is not significant and cannot be predicted At the same time, only less than 10% of patients can have long-term response Photo source: Nature Medicine to understand the determinants of glioma patients' response to immunosuppressive checkpoint inhibitors Researchers from Columbia University tracked 66 patients with glioma treated with standard PD-1 inhibitors (nivolumab or pembrolizumab), including 17 with long-term response Genomic and transcriptome analysis showed that PTEN mutations associated with immunosuppressive signal expression increased significantly in unresponsive tumors, and tumor cells carrying PTEN mutations were more closely connected with each other, preventing immune cells from infiltrating into tumor and tumor microenvironment On the contrary, MAPK signaling pathway (PTPN11, BRAF) mutations were more frequent in the tumor of responders "These mutations existed before patients were treated with PD-1 inhibitors, so testing for these mutations may provide biomarkers that predict whether patients will respond to immunotherapy." Fabio M Iwamoto, Ph.D., a professor of neurooncology at Columbia University and the author of the study At the same time, the researchers also found that the responsive tumors were related to the elimination of tumor epitopes, the diversity of T cell clones and the bifurcation of evolution patterns caused by tumor microenvironment The study also suggests that patients with MAPK mutations may benefit more from a combination of PD-1 inhibitors and MAPK targeted therapies MAPK targeted therapies have been approved for melanoma and are currently being tested for other cancers "We are still in the initial stage of understanding tumor immunotherapy, especially for glioma." Said Rabadan "But our research shows that we may be able to predict which patients might benefit from these therapies We have also identified new targets that may improve the efficacy of immunotherapy in all glioma patients " Reference: Raul Rabadan et al Immune and genomic correlates of response to anti-PD-1 immunotherapy in glioblastoma.Nature Medicine DOI:https://doi.org/10.1038/s41591-019-0349-y