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The immunomodulatory functions of RNA\u2010binding motif (RBM) proteins remain poorly understood. Using in vivo and in vitro models of RBM10 deficiency combined with cytokine arrays, CLIP\u2010seq, RIP, and proteomics, we found that RBM10 deficiency promotes an immunosuppressive microenvironment, and targeting key chemokines restored anti\u2010PD\u20101 efficacy in RBM10\u2010deficient LUAD models. RBM10 deficiency enhanced the polarization and recruitment of M2 tumor\u2010associated macrophages (TAMs), both in vitro and in vivo. Mechanistically, RBM10 loss disrupted STING exon 3 exclusion via alternative splicing and impaired QKI\u2010mediated stabilization of the STING\u2010E3(\u2010) isoform, shifting the splicing balance toward the STING\u2010E3(+) isoform and promoting CCL7 secretion. CCL7 acted through its receptor CCR2 on macrophages, driving M2 polarization and recruitment. This central pathway was further reinforced by a positive feedback loop wherein M2\u2010polarized TAMs transferred mitochondria to tumor cells, potentially contributing to mtDNA\u2010cGAS\u2010STING signaling and sustained CCL7 production. Therapeutically, CCL7\/CCR2 blockade synergized with PD\u20101 inhibition to promote tumor regression in RBM10\u2010deficient tumors. Collectively, RBM10 serves as a key immunoregulator in LUAD by modulating the STING\u2010CCL7\u2010CCR2 axis, and targeting the CCL7\u2010CCR2 axis represents a promising strategy to overcome anti\u2010PD\u20101 resistance.<\/jats:p>","DOI":"10.1002\/advs.202522159","type":"journal-article","created":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T10:00:01Z","timestamp":1782122401000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["RBM10 Deficiency Promotes Anti\u2010PD\u20101 Resistance in LUAD via STING Alternative Splicing\u2010Driven CCL7 Signaling and Macrophage Polarization"],"prefix":"10.1002","volume":"13","author":[{"given":"Weitong","family":"Gao","sequence":"first","affiliation":[{"name":"Department of Oncology Harbin Medical University Cancer Hospital  Harbin Heilongjiang 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