Integrated genomic analysis identifies a genetic mutation model predicting response to immune checkpoint inhibitors in melanoma

xloma.fota13 shared this article with you from Inoreader Integrated genomic analysis identifies a genetic mutation model predicting response to immune checkpoint inhibitors in melanoma Via Cancer Medicine This study provided evidences that the genetic mutation model (named as ITS) identified a melanoma population with multiple genetic patterns of sensitivity to ICIs, who might potentially benefit from ICIs therapy. Preliminary data from three independent cohorts strongly suggested better treatment outcomes from ICIs therapy in melanoma patients with high ITS. Remarkably, the combination strategy of ITS and TMB or LDH showed better prediction efficacy compared with any single biomarker. Abstract Several biomarkers such as tumor mutation burden (TMB), neoantigen load (NAL), programmed cell‐death receptor 1 ligand (PD‐L1) expression, and lactate dehydrogenase (LDH) have been developed for predicting response to immune checkpoint inhibitors (ICIs) in melanoma. However, some limitations including the undefined cut‐off value, poor uniformity of test platform, and weak reliability of prediction have restricted the broad application in clinical practice. In order to identify a clinically actionable biomarker and explore an effective strategy for prediction, we developed a genetic mutation model named as immunotherapy score (ITS) for predicting response to ICIs therapy in melanoma, based on whole‐exome sequencing data from previous studies. We observed that patients with high ITS had better durable clinical benefit and survival outcomes than patients with low ITS in three independent cohorts, as well as in the meta‐cohort. Notably, the prediction capability of ITS was m ore robust than that of TMB. Remarkably, ITS was not only an independent predictor of ICIs therapy, but also combined with TMB or LDH to better predict response to ICIs than any single biomarker. Moreover, patients with high ITS harbored the immunotherapy‐sensitive characteristics including high TMB and NAL, ultraviolet light damage, impaired DNA damage repair pathway, arrested cell cycle signaling, and frequent mutations in NF1 and SERPINB3/4. Overall, these findings deserve prospective investigation in the future and may help guide clinical decisions on ICIs therapy for patients with melanoma. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.