The browser you are using is not supported by this website. All versions of Internet Explorer are no longer supported, either by us or Microsoft (read more here: https://www.microsoft.com/en-us/microsoft-365/windows/end-of-ie-support).

Please use a modern browser to fully experience our website, such as the newest versions of Edge, Chrome, Firefox or Safari etc.

Kristian Pietras

Kristian Pietras

Research team manager

Kristian Pietras

Tertiary lymphoid structures improve immunotherapy and survival in melanoma

Author

  • 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
Show all

Summary, in English

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.

Department/s

  • LUCC: Lund University Cancer Centre
  • Melanoma Genomics
  • Breastcancer-genetics
  • The Liquid Biopsy and Tumor Progression in Breast Cancer
  • Therapeutic pathology
  • Lund Melanoma Study Group
  • EpiHealth: Epidemiology for Health
  • Experimental oncology

Publishing year

2020

Language

English

Pages

561-565

Publication/Series

Nature

Volume

577

Issue

7791

Document type

Journal article

Publisher

Nature Publishing Group

Topic

  • Cancer and Oncology

Status

Published

Project

  • MISS (Melanoma in Southern Sweden) population based cohort of 40 000 women

Research group

  • Melanoma Genomics
  • The Liquid Biopsy and Tumor Progression in Breast Cancer
  • Lund Melanoma Study Group
  • Experimental oncology

ISBN/ISSN/Other

  • ISSN: 0028-0836