Tertiary lymphoid structures improve immunotherapy and survival in melanoma

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

  • Rita Cabrita, Lunds Universitet
  • ,
  • Martin Lauss, Lunds Universitet
  • ,
  • Adriana Sanna, Lunds Universitet
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  • Marco Donia, University of Copenhagen
  • ,
  • Mathilde Skaarup Larsen, University of Copenhagen
  • ,
  • Shamik Mitra, Lunds Universitet
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  • Iva Johansson, Lunds Universitet
  • ,
  • Bengt Phung, Lunds Universitet
  • ,
  • Katja Harbst, Lunds Universitet
  • ,
  • Johan Vallon-Christersson, Lunds Universitet
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  • Alison van Schoiack, NanoString Technologies
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  • Kristina Lövgren, Lunds Universitet
  • ,
  • Sarah Warren, NanoString Technologies
  • ,
  • Karin Jirström, Lunds Universitet
  • ,
  • Håkan Olsson, Lunds Universitet
  • ,
  • Kristian Pietras, Lunds Universitet
  • ,
  • Christian Ingvar, Lund University
  • ,
  • Karolin Isaksson, Lund University
  • ,
  • Dirk Schadendorf, University of Duisburg-Essen
  • ,
  • Henrik Schmidt
  • Lars Bastholt, University of Southern Denmark
  • ,
  • Ana Carneiro, Lunds Universitet, Lund University
  • ,
  • Jennifer A. Wargo, University of Texas MD Anderson Cancer Center
  • ,
  • Inge Marie Svane, University of Copenhagen
  • ,
  • Göran Jönsson, Lunds Universitet

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
Issue7791
Pages (from-to)561-565
Number of pages5
ISSN0028-0836
DOIs
Publication statusPublished - 2020

    Research areas

  • CELLS, DYNAMICS, EXPRESSION

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