{"title":"NK cells link immune-checkpoint blockade immunotherapy and response in melanoma brain metastases.","authors":"Gary Kohanbash, Stephen C Frederico, Itay Raphael","doi":"10.1136/jitc-2025-011581","DOIUrl":null,"url":null,"abstract":"<p><p>Melanoma brain metastases (BMs) pose a significant clinical challenge. This commentary highlights the emerging understanding of the mechanisms behind immune-checkpoint blockade (ICB) efficacy in melanoma BMs. Specifically, we focus on a recent study by Fife <i>et al</i>, which revealed a non-canonical role for natural killer (NK) cells in shaping the tumor microenvironment following ICB therapy against melanoma BMs. Instead of direct tumor cell killing, this study demonstrates that ICB triggers NK cell chemokine release, CD8 T cell recruitment and enhanced antitumor immunity. The findings from this study highlight that the ICB mechanisms of action are complex and extend beyond the direct interference of inhibitor receptor-ligand interactions between cytotoxic CD8 T cells and tumor cells.</p>","PeriodicalId":14820,"journal":{"name":"Journal for Immunotherapy of Cancer","volume":"13 3","pages":""},"PeriodicalIF":10.3000,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11927483/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal for Immunotherapy of Cancer","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1136/jitc-2025-011581","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Melanoma brain metastases (BMs) pose a significant clinical challenge. This commentary highlights the emerging understanding of the mechanisms behind immune-checkpoint blockade (ICB) efficacy in melanoma BMs. Specifically, we focus on a recent study by Fife et al, which revealed a non-canonical role for natural killer (NK) cells in shaping the tumor microenvironment following ICB therapy against melanoma BMs. Instead of direct tumor cell killing, this study demonstrates that ICB triggers NK cell chemokine release, CD8 T cell recruitment and enhanced antitumor immunity. The findings from this study highlight that the ICB mechanisms of action are complex and extend beyond the direct interference of inhibitor receptor-ligand interactions between cytotoxic CD8 T cells and tumor cells.
期刊介绍：
The Journal for ImmunoTherapy of Cancer (JITC) is a peer-reviewed publication that promotes scientific exchange and deepens knowledge in the constantly evolving fields of tumor immunology and cancer immunotherapy. With an open access format, JITC encourages widespread access to its findings. The journal covers a wide range of topics, spanning from basic science to translational and clinical research. Key areas of interest include tumor-host interactions, the intricate tumor microenvironment, animal models, the identification of predictive and prognostic immune biomarkers, groundbreaking pharmaceutical and cellular therapies, innovative vaccines, combination immune-based treatments, and the study of immune-related toxicity.
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