{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T19:26:06Z","timestamp":1792178766160,"version":"4.4.0"},"reference-count":35,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T00:00:00Z","timestamp":1755043200000},"content-version":"vor","delay-in-days":12,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81972169"],"award-info":[{"award-number":["81972169"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82141101"],"award-info":[{"award-number":["82141101"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Respiratory J"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Interleukin\u201015 (IL\u201015) is a pleiotropic cytokine recognized as a promising therapeutic agent in cancer immunotherapy. IL\u201015 superagonists have shown efficacy across various cancers, yet their effects in lung cancer immunotherapy remain underexplored.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This study evaluated the antitumor effects of SHR\u20101501 through intratumoral injection in two murine lung cancer models: Lewis lung carcinoma (LLC) and Kras G12D\/p53\u2212\/\u2212 (KP). We employed flow cytometry to assess immune cell populations in the tumor microenvironment (TME) and systemic circulation. Immunohistochemistry (IHC) was used to analyze TME changes in tumor tissues, while single\u2010cell RNA sequencing provided insights into TME modulation following SHR\u20101501 treatment. Additionally, we assessed the synergistic potential of combining SHR\u20101501 with PD\u20101 monoclonal antibody (mAb) therapy and explored the abscopal effect of SHR\u20101501.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>SHR\u20101501 significantly inhibited tumor growth in both KP and LLC models at 5\u2009\u03bcg and 15\u2009\u03bcg doses (<jats:italic>p<\/jats:italic>\u2009=\u20090.0022 and <jats:italic>p<\/jats:italic>\u2009=\u20090.0002, respectively, for KP; <jats:italic>p<\/jats:italic>\u2009=\u20090.0508 and <jats:italic>p<\/jats:italic>\u2009=\u20090.0131, respectively, for LLC). Flow cytometry revealed increased infiltration of CD8+ T cells, effector memory CD8+ T cells (TEM), and natural killer (NK) cells in the TME. SHR\u20101501 also enhanced systemic immune responses, increasing CD8+ T cells and TEM populations in peripheral blood and spleen, with an early NK cell elevation on day 7 post\u2010treatment. Single\u2010cell analysis indicated that SHR\u20101501 promoted the activity of macrophages, increasing M1 macrophage proportions. Moreover, SHR\u20101501 enhanced the antitumor immune response by promoting pro\u2010inflammatory changes across multiple cell types within the TME, including neutrophils, fibroblasts, and endothelial cells. When combined with PD\u20101mAb, SHR\u20101501 exhibited potent synergistic antitumor effects. The combination therapy significantly prolonged overall survival with no significant toxicity observed. Furthermore, SHR\u20101501 may have the ability to induce an abscopal effect.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>SHR\u20101501 demonstrated potent antitumor activity, especially when combined with PD\u20101 mAb. Its mechanism likely involves promoting CD8+ T cell and NK cell infiltration and enhancing M1 macrophage activity. These findings provide evidence for further clinical trials exploring SHR\u20101501 in nonsmall cell lung cancer (NSCLC) therapy.<\/jats:p><\/jats:sec>","DOI":"10.1111\/crj.70117","type":"journal-article","created":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T08:46:09Z","timestamp":1755074769000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["IL\u201015 Superagonist SHR\u20101501 Enhances Immune Responses in Lung Cancer by Modulating Tumor Microenvironment"],"prefix":"10.1111","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3794-0499","authenticated-orcid":false,"given":"Qian","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Lung Cancer and Immunology, Shanghai Pulmonary Hospital School of Medicine, Tongji University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Congli","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Lung Cancer and Immunology, Shanghai Pulmonary Hospital School of Medicine, Tongji University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minlin","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Lung Cancer and Immunology, Shanghai Pulmonary Hospital School of Medicine, Tongji University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Lung Cancer and Immunology, Shanghai Pulmonary Hospital School of Medicine, Tongji University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heng","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Shanghai Pulmonary Hospital School of Medicine, Tongji University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuefei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Lung Cancer and Immunology, Shanghai Pulmonary Hospital School of Medicine, Tongji University  Shanghai 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