{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T08:59:58Z","timestamp":1790758798014,"version":"4.1.0"},"reference-count":61,"publisher":"BMJ","issue":"9","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"content-version":"unspecified","delay-in-days":2,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82473187"],"award-info":[{"award-number":["82473187"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"High-level Talent Introduction Project of Fujian Cancer Hospital","award":["F2328R-GC301-01"],"award-info":[{"award-number":["F2328R-GC301-01"]}]},{"DOI":"10.13039\/501100003392","name":"Natural Science Foundation of Fujian Province","doi-asserted-by":"publisher","award":["2025J01225"],"award-info":[{"award-number":["2025J01225"]}],"id":[{"id":"10.13039\/501100003392","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2026,8,17]]},"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Tertiary lymphoid structures (TLS) are spatially organized immune niches associated with therapeutic response and favorable outcomes in breast cancer (BC). However, TLS assessment currently relies on invasive tissue-based analyses, and the biological mechanisms underlying imaging-based TLS prediction remain poorly understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We developed and validated a spatial heterogeneity-based radiomic TLS signature (shTLS) using dynamic contrast-enhanced MRI to non-invasively predict TLS status across multicenter BC cohorts. Spatial habitat radiomics were used to capture intratumoral and peritumoral immune-related heterogeneity. Integrated multi-omics analyses, including transcriptomics, pathomics, genomics, single-cell RNA sequencing, immunohistochemistry, and multiplex immunofluorescence, were performed to biologically interpret shTLS-defined subgroups. Functional drug-sensitivity assays were conducted to assess therapeutic implications.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The shTLS model achieved robust predictive performance across independent cohorts and molecular subtypes. High shTLS scores were associated with immune-inflamed tumors characterized by spatially clustered activated T cells and dendritic cells (DCs). In contrast, shTLS-low tumors exhibited an immunosuppressive spatial niche with peripheral accumulation of CD4\n                      <jats:sup>+<\/jats:sup>\n                      PD-1\n                      <jats:sup>+<\/jats:sup>\n                      T cells and plasma cells, increased immune-tumor separation, and enhanced inflammatory and immunoregulatory signaling. An indoleamine 2,3-dioxygenase 1 (IDO1)-associated immunoregulatory program was observed in the shTLS-low tumors, which appeared to be preferentially expressed by LAMP3\n                      <jats:sup>+<\/jats:sup>\n                      CCR7\n                      <jats:sup>+<\/jats:sup>\n                      migratory DCs. Pharmacologic inhibition of IDO1 enhanced chemotherapy and CDK4\/6 inhibitor sensitivity in vitro.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study establishes spatial radiomics as a non-invasive approach to decode TLS-associated immune ecosystems and supports the presence of an IDO1-associated immunosuppressive phenotype, providing biological insight and translational rationale for patient stratification and future combination strategies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jitc-2026-015224","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T13:50:25Z","timestamp":1788443425000},"page":"e015224","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Spatial habitat radiomics predicts tertiary lymphoid structure status and identifies an IDO1\n                    <sup>+<\/sup>\n                    migratory dendritic cell axis in breast cancer"],"prefix":"10.1136","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-2494-4981","authenticated-orcid":false,"given":"Yushuai","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Breast Surgery, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, Fujian, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9243-337X","authenticated-orcid":false,"given":"Qing","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Breast Surgery, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, Fujian, 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