ArticleClinical cancer research : an official journal of the American Association for Cancer Research2025
Chemotherapy Drives Tertiary Lymphoid Structures That Correlate with ICI-Responsive TCF1+CD8+ T Cells in Metastatic Ovarian Cancer.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Immune checkpoint inhibitor integration in locoregionally advanced nasopharyngeal carcinoma: a prospective evidence synthesis on efficacy, safety, and therapeutic optimization.Frontiers in immunology · 2026Pooled it
- Migration of immune cells in tumors and inflammation: molecular mechanisms and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- A tumor profiling resource for ovarian cancer: insights into chemotherapy-driven heterogeneity and personalized treatment strategy.Nature communications · 2026Article
- Tertiary lymphoid structures in breast cancer: Mechanistic insights, subtype-specific patterns, and therapeutic implications.World journal of surgical oncology · 2026Review
- NKG2A inhibition promotes NK cell-CD8Nature communications · 2026Article
- Immunogenic cell death as a cornerstone for combination therapies with immune checkpoint blockade.Molecular cancer · 2026Review
- The life cycle of tertiary lymphoid structures in pancreatic cancer-a window of opportunity for immunotherapy.Frontiers in immunology · 2026Review
- Follicular T cells in the ovarian cancer immune microenvironment: biological insights and translational implications.Frontiers in immunology · 2026Review
- Mechanistic roles and clinical applications of tertiary lymphoid structures in colorectal cancer drug resistance.Cancer drug resistance (Alhambra, Calif.) · 2026Review
- Tertiary lymphoid structures in neoadjuvant and perioperative cancer immunotherapy: a review and proposed framework for biomarker interpretation and validation.Frontiers in immunology · 2026Review
- Initiation of Tertiary Lymphoid Structures for Cancer Immunotherapy.Research (Washington, D.C.) · 2026Review
- Neoadjuvant chemotherapy-induced immune remodeling in ovarian cancer: implications for TIL dynamics and combination immunotherapy.Frontiers in immunology · 2026Review
- Research progress of tertiary lymphoid structure in hepatocellular carcinoma: from prognostic biomarkers to new strategies for immunotherapy.Frontiers in immunology · 2026Review
- Tertiary lymphoid structures are associated with lower axillary residual nodal burden in breast cancer patients after neoadjuvant chemotherapy.European journal of medical research · 2025Article
- Ovarian cancer metastasis to the human omentum disrupts organ homeostasis and induces fundamental tissue reprogramming.Nature communications · 2025Article
- SM08502-Mediated β-Catenin Repression Synergizes with Olaparib to Inhibit Tumor Progression.Cancer research communications · 2025Article
- Tertiary lymphoid structures in cancer: spatiotemporal heterogeneity, immune orchestration, and translational opportunities.Journal of hematology & oncology · 2025Review
- Immunocompetent C57BL/6 syngeneic mouse ovarian cancer models with defined genetic alterations.Scientific reports · 2025Article
- Role of tertiary lymphoid structures in the tumour microenvironment and immunotherapy response of renal cell carcinoma.Clinical and translational medicine · 2025Review
- Enhanced formation of tertiary lymphoid structures shapes the anti-tumor microenvironment in hepatocellular carcinoma after FOLFOX-HAIC therapy.Cell reports. Medicine · 2025Article
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Authors and funding
28 authors.
Funding
Abstract
purposePatients with high-grade serous ovarian carcinoma (HGSOC) are virtually insensitive to immune checkpoint inhibitors (ICI) employed as standalone therapeutics, at least in part reflecting microenvironmental immunosuppression. Thus, conventional chemotherapeutics and targeted anticancer agents that not only mediate cytotoxic effects but also promote the recruitment of immune effector cells to the HGSOC microenvironment stand out as promising combinatorial partners for ICIs in this oncological indication. EXPERIMENTAL
designWe harnessed a variety of transcriptomic, spatial, and functional assays to characterize the differential impact of neoadjuvant paclitaxel-carboplatin on the immunological configuration of paired primary and metastatic HGSOC biopsies as compared to neoadjuvant chemotherapy (NACT)-naïve HGSOC samples from five independent patient cohorts.
resultsWe found NACT-driven endoplasmic reticulum stress and calreticulin exposure in metastatic HGSOC lesions culminates with the establishment of a dense immune infiltrate including follicular T cells (TFH cells), a prerequisite for mature tertiary lymphoid structure (TLS) formation. In this context, TLS maturation was associated with an increased intratumoral density of ICI-sensitive TCF1+PD1+ CD8+ T cells over their ICI-insensitive TIM-3+PD1+ counterparts. Consistent with this notion, chemotherapy coupled with a PD1-targeting ICI provided a significant survival benefit over either therapeutic approach in syngeneic models of HGSOC bearing high (but not low) tumor mutational burden.
conclusionsAltogether, our findings suggest that NACT promotes TLS formation and maturation in HGSOC lesions, de facto preserving an intratumoral ICI-sensitive T-cell phenotype. These observations emphasize the role of rational design, especially relative to the administration schedule, for clinical trials testing chemotherapy plus ICIs in patients with HGSOC. See related commentary by Bravo Melgar and Laoui, p. 10.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.