Tertiary lymphoid structures improve immunotherapy and survival in melanoma
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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Tertiary lymphoid structures improve immunotherapy and survival in melanoma. / Cabrita, Rita; Lauss, Martin; Sanna, Adriana; Donia, Marco; Skaarup Larsen, Mathilde; Mitra, Shamik; Johansson, Iva; Phung, Bengt; Harbst, Katja; Vallon-Christersson, Johan; van Schoiack, Alison; Lövgren, Kristina; Warren, Sarah; Jirström, Karin; Olsson, Håkan; Pietras, Kristian; Ingvar, Christian; Isaksson, Karolin; Schadendorf, Dirk; Schmidt, Henrik; Bastholt, Lars; Carneiro, Ana; Wargo, Jennifer A.; Svane, Inge Marie; Jönsson, Göran.
I: Nature, Bind 577, 2020, s. 561-565.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Tertiary lymphoid structures improve immunotherapy and survival in melanoma
AU - Cabrita, Rita
AU - Lauss, Martin
AU - Sanna, Adriana
AU - Donia, Marco
AU - Skaarup Larsen, Mathilde
AU - Mitra, Shamik
AU - Johansson, Iva
AU - Phung, Bengt
AU - Harbst, Katja
AU - Vallon-Christersson, Johan
AU - van Schoiack, Alison
AU - Lövgren, Kristina
AU - Warren, Sarah
AU - Jirström, Karin
AU - Olsson, Håkan
AU - Pietras, Kristian
AU - Ingvar, Christian
AU - Isaksson, Karolin
AU - Schadendorf, Dirk
AU - Schmidt, Henrik
AU - Bastholt, Lars
AU - Carneiro, Ana
AU - Wargo, Jennifer A.
AU - Svane, Inge Marie
AU - Jönsson, Göran
PY - 2020
Y1 - 2020
N2 - 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.
AB - 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.
UR - https://www.nature.com/articles/s41586-020-2155-6
U2 - 10.1038/s41586-019-1914-8
DO - 10.1038/s41586-019-1914-8
M3 - Journal article
C2 - 31942071
AN - SCOPUS:85078123517
VL - 577
SP - 561
EP - 565
JO - Nature
JF - Nature
SN - 0028-0836
ER -
ID: 255736447