{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T01:37:28Z","timestamp":1783647448246,"version":"3.55.0"},"reference-count":13,"publisher":"BMJ","issue":"4","license":[{"start":{"date-parts":[[2025,4,16]],"date-time":"2025-04-16T00:00:00Z","timestamp":1744761600000},"content-version":"unspecified","delay-in-days":15,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2025,4,1]]},"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:p>Tertiary lymphoid structures (TLS) are ectopic lymphoid aggregates that allow for optimal B-T cell crosstalk in solid tumors. Further, TLS are found in many solid tumors and are associated with improved patient survival and superior immunotherapeutic response, ultimately reflecting their potential as new therapeutic targets. Despite the prognostic benefit of TLS, women with high-grade serous ovarian cancer (HGSOC) are insensitive to immunotherapies. We have summarized recent work on TLS in patients with HGSOC, ultimately demonstrating how tumor microenvironment factors and therapeutics shape the organization and maturation of TLS. Specifically, TLS function varies across anatomical sites, with more germinal center (GC)+TLS with active B cells found in tumors within the omentum and fallopian tube compared with ovary. Further, cancer-associated stromal cells within patients negate the prognostic benefit of TLS and reduce B cell recruitment and function with blunted differentiation of follicular dendritic cells, which lay the foundation for functional GCs. Neoadjuvant chemotherapy (NACT) also impacts the HGSOC microenvironment, with metastatic tumors showing increased infiltration of effector immune cells (primarily TCF1+PD1+ CD8+ T cells) and \u201cmature\u201d TLS formation compared with NACT-na\u00efve patients. These findings provide a rationale for designing therapeutics targeting the HGSOC TLS landscape and restoring immunotherapeutic responses in these patients.<\/jats:p>","DOI":"10.1136\/jitc-2025-011670","type":"journal-article","created":{"date-parts":[[2025,4,17]],"date-time":"2025-04-17T20:15:21Z","timestamp":1744920921000},"page":"e011670","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":5,"title":["Past failures and new horizons: the nuances of tertiary lymphoid structures in high-grade serous ovarian cancer may contribute to immunotherapy effectiveness"],"prefix":"10.1136","volume":"13","author":[{"given":"Rufiaat","family":"Rashid","sequence":"first","affiliation":[{"name":"University of Pittsburgh, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lan","family":"Coffman","sequence":"additional","affiliation":[{"name":"University of Pittsburgh\/UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tullia C","family":"Bruno","sequence":"additional","affiliation":[{"name":"University of Pittsburgh, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian","family":"MacFawn","sequence":"additional","affiliation":[{"name":"Department of Biology, Grove City College, Grove City, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2025,4,17]]},"reference":[{"key":"2025100301162362000_13.4.e011670.1","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-024-00728-0"},{"key":"2025100301162362000_13.4.e011670.2","doi-asserted-by":"crossref","unstructured":"MacFawn IP , Bruno TC . Tertiary lymphoid structure formation and function in the tumor microenvironment. In: Rezaei N , ed. Handbook of cancer and immunology. Springer International Publishing, 2022: 1\u201331. 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