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Although immune checkpoint inhibitors (ICIs) have demonstrated efficacy in treating NSCLC\u2010BM, their clinical benefits are often limited. The combination of radiotherapy (RT) and ICIs has emerged as a promising strategy for overcoming these challenges. This review summarizes the current knowledge regarding the immune landscape of NSCLC\u2010BM as well as the clinical evidence supporting and challenging the RT\u2013ICI combination, and it provides an expanded mechanistic framework detailing how RT reshapes the tumor immune microenvironment. RT can enhance the antitumor immune response by disrupting the blood\u2013brain barrier, reprogramming the tumor microenvironment, and improving immune cell infiltration. Clinical studies have supported the synergistic potential of RT and ICIs against NSCLC\u2010BM, showing improved survival and progression\u2010free survival rates. However, challenges such as resistance and toxicity remain, and further investigation is required to refine treatment strategies. We further discuss optimal RT fractionation and sequencing strategies, toxicity mitigation, including practical approaches for managing radiation necrosis, and emerging biomarkers that may guide personalized treatment. A clearer understanding of these biological and clinical interactions is essential to refine treatment algorithms and maximize the therapeutic potential of radioimmunotherapy in NSCLC\u2010BM.<\/jats:p>","DOI":"10.1002\/pro6.70085","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T10:56:56Z","timestamp":1786964216000},"page":"403-416","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Synergistic effects and clinical utilization of radioimmunotherapy for brain metastases from driver mutation\u2010negative non\u2010small cell lung cancer"],"prefix":"10.1002","volume":"10","author":[{"given":"Silai","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology Fudan University Shanghai Cancer Center  Shanghai China"},{"name":"Department of Oncology Shanghai Medical College, Fudan University  Shanghai China"},{"name":"Shanghai Clinical Research Center for 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