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Here, we demonstrate that high-grade serous ovarian carcinoma (HGSOC) contains distinct immune aggregates with varying degrees of organization and maturation. Specifically, mature TLSs (mTLS) as forming only in 16% of HGSOCs with relatively elevated tumor mutational burden (TMB) are associated with an increased intratumoral density of CD8<jats:sup>+<\/jats:sup> effector T (T<jats:sub>EFF<\/jats:sub>) cells and TIM3<jats:sup>+<\/jats:sup>PD1<jats:sup>+<\/jats:sup>, hence poorly immune checkpoint inhibitor (ICI)-sensitive, CD8<jats:sup>+<\/jats:sup> T cells. Conversely, CD8<jats:sup>+<\/jats:sup> T cells from immunologically hot tumors like non-small cell lung carcinoma (NSCLC) are enriched in ICI-responsive TCF1<jats:sup>+<\/jats:sup> PD1<jats:sup>+<\/jats:sup> T cells. Spatial B-cell profiling identifies patterns of in situ maturation and differentiation associated with mTLSs. Moreover, B-cell depletion promotes signs of a dysfunctional CD8<jats:sup>+<\/jats:sup> T cell compartment among tumor-infiltrating lymphocytes from freshly isolated HGSOC and NSCLC biopsies. Taken together, our data demonstrate that \u2013 at odds with NSCLC \u2013 HGSOC is associated with a low density of follicular helper T cells and thus develops a limited number of mTLS that might be insufficient to preserve a ICI-sensitive TCF1<jats:sup>+<\/jats:sup>PD1<jats:sup>+<\/jats:sup> CD8<jats:sup>+<\/jats:sup> T cell phenotype. These findings point to key quantitative and qualitative differences between mTLSs in ICI-responsive vs ICI-irresponsive neoplasms that may guide the development of alternative immunotherapies for patients with HGSOC.<\/jats:p>","DOI":"10.1038\/s41467-024-46873-w","type":"journal-article","created":{"date-parts":[[2024,3,21]],"date-time":"2024-03-21T12:02:08Z","timestamp":1711022528000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":113,"title":["Tertiary lymphoid structures and B cells determine clinically relevant T cell phenotypes in ovarian 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