{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,21]],"date-time":"2026-06-21T02:13:50Z","timestamp":1782008030304,"version":"3.54.5"},"reference-count":9,"publisher":"BMJ","issue":"3","license":[{"start":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T00:00:00Z","timestamp":1742342400000},"content-version":"unspecified","delay-in-days":18,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2025,3,10]]},"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats: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 <jats:italic>et al<\/jats:italic>, 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\u2013ligand interactions between cytotoxic CD8 T cells and tumor cells.<\/jats:p>","DOI":"10.1136\/jitc-2025-011581","type":"journal-article","created":{"date-parts":[[2025,3,21]],"date-time":"2025-03-21T03:43:04Z","timestamp":1742528584000},"page":"e011581","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":6,"title":["NK cells link immune-checkpoint blockade immunotherapy and response in melanoma brain metastases"],"prefix":"10.1136","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3953-8022","authenticated-orcid":false,"given":"Gary","family":"Kohanbash","sequence":"first","affiliation":[{"name":"Department of Neurological Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"},{"name":"Department of Immunology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"},{"name":"University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen C.","family":"Frederico","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"},{"name":"University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7369-2752","authenticated-orcid":false,"given":"Itay","family":"Raphael","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"},{"name":"University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2025,3,18]]},"reference":[{"key":"2025100310025015000_13.3.e011581.1","doi-asserted-by":"crossref","first-page":"1390","DOI":"10.1002\/cncr.32714","article-title":"Current multidisciplinary management of brain metastases","volume":"126","author":"Moravan","year":"2020","journal-title":"Cancer"},{"key":"2025100310025015000_13.3.e011581.2","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.trecan.2018.01.003","article-title":"The Evolving Landscape of Brain Metastasis","volume":"4","author":"Valiente","year":"2018","journal-title":"Trends Cancer"},{"key":"2025100310025015000_13.3.e011581.3","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1805453"},{"key":"2025100310025015000_13.3.e011581.4","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(16)30053-5"},{"key":"2025100310025015000_13.3.e011581.5","doi-asserted-by":"crossref","DOI":"10.1172\/JCI169314","article-title":"Immune checkpoint blockade induces distinct alterations in the microenvironments of primary and metastatic brain tumors","volume":"133","author":"Sun","year":"2023","journal-title":"J Clin Invest"},{"key":"2025100310025015000_13.3.e011581.6","doi-asserted-by":"crossref","first-page":"3051","DOI":"10.1172\/JCI133353","article-title":"Minimal PD-1 expression in mouse and human NK cells under diverse conditions","volume":"130","author":"Judge","year":"2020","journal-title":"J Clin Invest"},{"key":"2025100310025015000_13.3.e011581.7","doi-asserted-by":"publisher","DOI":"10.1172\/JCI99317"},{"key":"2025100310025015000_13.3.e011581.8","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1714089115"},{"key":"2025100310025015000_13.3.e011581.9","doi-asserted-by":"crossref","DOI":"10.1136\/jitc-2024-009522","article-title":"Natural killer cells are required for the recruitment of CD8+ T cells and the efficacy of immune checkpoint blockade in melanoma brain metastases","volume":"12","author":"Fife","year":"2024","journal-title":"J Immunother Cancer"}],"container-title":["Journal for ImmunoTherapy of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jitc-2025-011581","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T17:03:01Z","timestamp":1759510981000},"score":1,"resource":{"primary":{"URL":"https:\/\/jitc.bmj.com\/lookup\/doi\/10.1136\/jitc-2025-011581"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3]]},"references-count":9,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,3,18]]},"published-print":{"date-parts":[[2025,3]]}},"alternative-id":["10.1136\/jitc-2025-011581"],"URL":"https:\/\/doi.org\/10.1136\/jitc-2025-011581","relation":{},"ISSN":["2051-1426"],"issn-type":[{"value":"2051-1426","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3]]}}}