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Our previous studies have shown that the expression of programmed cell death 1 ligand 1 (PD\u2010L1) is upregulated following MWA, suggesting that MWA combined with anti\u2010PD\u2010L1 treatment can serve as a promising clinical therapeutic strategy against cancer. Using MWA\u2010treated preclinical mice models, MWA combined with \u03b1PD\u2010L1 treatment decreased tumor growth and prolonged overall survival (OS). Furthermore, through flow cytometry and single\u2010cell RNA sequencing analysis, we determined that the MWA plus \u03b1PD\u2010L1 therapy significantly suppressed CD8<jats:sup>+<\/jats:sup> T cell exhaustion and enhanced their effector function. A significant increase in \u03b3\u2010interferon (IFN\u2010\u03b3) stimulated transcription factors, specifically Irf8, was observed. This enhancement facilitated the polarization of tumor\u2010associated macrophages (TAM1s and TAM2s) through the nuclear factor\u2010\u03baB\/JAK\u2010STAT1 signaling pathway. Furthermore, the combination therapy stimulated the production of CXC motif chemokine ligand (CXCL9) by TAM1s and tumor cells, potentially increasing the chemotaxis of CD8 T cells and Th1 cells. Knocking out Cxcl9 in MC38 tumor cells or using CXCL9 blockade enhanced tumor growth of untreated tumors and shortened OS. Taken together, our study showed that blocking the IFN\u2010\u03b3\u2010Cxcl9\u2010CD8<jats:sup>+<\/jats:sup> T axis promoted tumor progression and discovered a potential involvement of IRF8\u2010regulated TAMs in preventing T cell exhaustion. Collectively, we identified that the combination of MWA with anti\u2010PD\u2010L1 treatment holds promise as a therapeutic strategy to rejuvenate the immune response against tumors. This merits further exploration in clinical studies.<\/jats:p>","DOI":"10.1111\/cas.16182","type":"journal-article","created":{"date-parts":[[2024,4,24]],"date-time":"2024-04-24T08:24:59Z","timestamp":1713947099000},"page":"2196-2208","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Microwave ablation combined with <scp>PD\u2010L1<\/scp> blockade synergistically promotes Cxcl9\u2010mediated antitumor immunity"],"prefix":"10.1111","volume":"115","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-3638-7800","authenticated-orcid":false,"given":"Ningning","family":"He","sequence":"first","affiliation":[{"name":"College of Medicine Yangzhou University  Yangzhou China"},{"name":"Department of Tumor Biological Treatment The Third Affiliated Hospital of Soochow University  Changzhou China"},{"name":"Institute of Cell Therapy The First People's Hospital of Changzhou  Changzhou 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