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The medicinal herb\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Centipeda minima<\/jats:italic>\n                    <\/jats:styled-content>\n                    has been traditionally employed to treat respiratory diseases and cancer; however, whether\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>C. minima<\/jats:italic>\n                    <\/jats:styled-content>\n                    and its bioactive constituents can activate CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell\u2010mediated antitumor immunity in non\u2010small cell lung cancer (NSCLC) remains elusive. In this study, the ethanol extract of\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>C. minima<\/jats:italic>\n                    <\/jats:styled-content>\n                    (ECM) significantly enhanced the cytotoxic activity of human peripheral blood mononuclear cell\u2010derived activated T cells and murine primary CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells against NSCLC cells, and promoted CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell infiltration in the LLC syngeneic tumor model. RNA\u2010seq profiling indicated that ECM potentially triggers type\u2010I interferon (IFN\u2010I)\u2010mediated innate immunity in NSCLC. Mechanistically, ECM treatment activated the cGAS\/STING pathway in NSCLC cells, as evidenced by increased phosphorylation of TBK1 and IRF3, elevated\n                    <jats:italic>IFN\u2010I<\/jats:italic>\n                    gene expression, and enhanced CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells activity. Notably, ECM markedly downregulated both mitochondrial and nuclear FANCD2 protein levels, which may facilitate cytosolic release of mitochondrial and nuclear DNA, thereby stimulating the cGAS\/STING\/IFN\u2010I signaling axis. ECM\u2010induced FANCD2 downregulation was markedly reversed by the proteasome inhibitor MG\u2010132. Combination treatment with ECM and anti\u2010PD\u20101 antibody synergistically suppressed tumor growth in the LLC syngeneic model, accompanied by elevated\n                    <jats:italic>IFN\u2010I<\/jats:italic>\n                    expression and pronounced recruitment of activated CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells. Moreover, 3\u2010\n                    <jats:italic>O<\/jats:italic>\n                    \u2010methylquercetin and several sesquiterpene lactones abundant in ECM were identified to downregulate FANCD2, activate TBK1\/IRF3 pathway, and enhance\n                    <jats:italic>IFN\u2010I<\/jats:italic>\n                    expression in NSCLC cells. Among these active compounds, arnicolide D promoted FANCD2 degradation in a proteasome\u2010dependent manner, whereas 3\u2010\n                    <jats:italic>O<\/jats:italic>\n                    \u2010methylquercetin predominantly suppressed FANCD2 gene expression. Collectively, our findings suggest that FANCD2 may serve as a novel therapeutic target for enhancing antitumor innate immunity, and that\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>C. minima<\/jats:italic>\n                    <\/jats:styled-content>\n                    along with its active compounds can potentiate antitumor immunotherapy by activating the FANCD2\u2010cGAS\/STING\/IFN\u2010I signaling axis.\n                  <\/jats:p>","DOI":"10.1002\/ptr.70460","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:05:10Z","timestamp":1790294710000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Identification of Active Compounds of\n                    <i>Centipeda minima<\/i>\n                    for Potentiating Tumor Immunotherapy in Non\u2010Small Cell Lung Cancer via\n                    <scp>FANCD2<\/scp>\n                    \u2010\n                    <scp>cGAS<\/scp>\n                    \/\n                    <scp>STING<\/scp>\n                    \/\n                    <scp>IFN<\/scp>\n                    \u2010I Signaling Axis"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-9987-0139","authenticated-orcid":false,"given":"Han\u2010Chen","family":"Wang","sequence":"first","affiliation":[{"name":"Key Laboratory of Chinese Medicinal Resource From Lingnan, Ministry of Education, School of Pharmaceutical Sciences Guangzhou University of Chinese Medicine  Guangzhou China"},{"name":"Research Center of Chinese Herbal Resource Science and Engineering, School of Pharmaceutical Sciences Guangzhou University of Chinese Medicine  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7640-2789","authenticated-orcid":false,"given":"Chu\u2010Ying","family":"Chen","sequence":"additional","affiliation":[{"name":"Key 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