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Tertiary lymphoid structures improve immunotherapy and survival in melanoma

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  1. Repositioning of the global epicentre of non-optimal cholesterol

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  2. Statin therapy is associated with lower prevalence of gut microbiota dysbiosis

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  3. Author Correction: Tertiary lymphoid structures improve immunotherapy and survival in melanoma

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  4. Analyses of non-coding somatic drivers in 2,658 cancer whole genomes

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  5. Patterns of somatic structural variation in human cancer genomes

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  1. Author Correction: Mutational and putative neoantigen load predict clinical benefit of adoptive T cell therapy in melanoma

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Author Correction: Tertiary lymphoid structures improve immunotherapy and survival in melanoma

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. CTLA-4 blockade boosts the expansion of tumor-reactive CD8+ tumor-infiltrating lymphocytes in ovarian cancer

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  4. Genome-wide CRISPR-Cas9 screening reveals ubiquitous T cell cancer targeting via the monomorphic MHC class I-related protein MR1

    Research output: Contribution to journalJournal articleResearchpeer-review

  • Rita Cabrita
  • Martin Lauss
  • Adriana Sanna
  • Marco Donia
  • Mathilde Skaarup Larsen
  • Shamik Mitra
  • Iva Johansson
  • Bengt Phung
  • Katja Harbst
  • Johan Vallon-Christersson
  • Alison van Schoiack
  • Kristina Lövgren
  • Sarah Warren
  • Karin Jirström
  • Håkan Olsson
  • Kristian Pietras
  • Christian Ingvar
  • Karolin Isaksson
  • Dirk Schadendorf
  • Henrik Schmidt
  • Lars Bastholt
  • Ana Carneiro
  • Jennifer A Wargo
  • Inge Marie Svane
  • Göran Jönsson
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Checkpoint blockade therapies that reactivate tumour-associated T cells can induce durable tumour control and result in the long-term survival of patients with advanced cancers1. Current predictive biomarkers for therapy response include high levels of intratumour immunological activity, a high tumour mutational burden and specific characteristics of the gut microbiota2,3. Although the role of T cells in antitumour responses has thoroughly been studied, other immune cells remain insufficiently explored. Here we use clinical samples of metastatic melanomas to investigate the role of B cells in antitumour responses, and find that the co-occurrence of tumour-associated CD8+ T cells and CD20+ B cells is associated with improved survival, independently of other clinical variables. Immunofluorescence staining of CXCR5 and CXCL13 in combination with CD20 reveals the formation of tertiary lymphoid structures in these CD8+CD20+ tumours. We derived a gene signature associated with tertiary lymphoid structures, which predicted clinical outcomes in cohorts of patients treated with immune checkpoint blockade. Furthermore, B-cell-rich tumours were accompanied by increased levels of TCF7+ naive and/or memory T cells. This was corroborated by digital spatial-profiling data, in which T cells in tumours without tertiary lymphoid structures had a dysfunctional molecular phenotype. Our results indicate that tertiary lymphoid structures have a key role in the immune microenvironment in melanoma, by conferring distinct T cell phenotypes. Therapeutic strategies to induce the formation of tertiary lymphoid structures should be explored to improve responses to cancer immunotherapy.

Original languageEnglish
JournalNature
Volume577
Issue number7791
Pages (from-to)561-565
Number of pages5
ISSN0028-0836
DOIs
Publication statusPublished - Jan 2020

ID: 59226917