B cells are associated with survival and immunotherapy response in sarcoma

Autor: Cheng-Ming Sun, Li Ping Hsiao, Jennifer A. Wargo, Hussein Abdul-Hassan Tawbi, Laetitia Lacroix, Carlo Lucchesi, Aurélien de Reyniès, Catherine Sautès-Fridman, Antoine Italiano, Khalid M. Wani, Marco Moreira, Christina L. Roland, Guillaume Lacroix, Denise K. Reinke, Ivo Natario, Antoine Bougoüin, Emily Z. Keung, Wei Lien Wang, Florent Petitprez, Julien Calderaro, Maud Toulmonde, Tom Wei-Wu Chen, Yung-Ming Jeng, Vanessa Bolejack, Julien Adam, Yec′han Laizet, Melissa Amber Burgess, Alexander J. Lazar, Wolf H. Fridman
Přispěvatelé: Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Université Sorbonne Paris Cité (USPC), (le programme) Cartes d'identité des tumeurs (CIT), Ligue Nationales Contre le Cancer (LNCC), The University of Texas M.D. Anderson Cancer Center [Houston], National Taiwan University [Taiwan] (NTU), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut Gustave Roussy (IGR), Institut Bergonié [Bordeaux], UNICANCER, University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE), Actions for OnCogenesis understanding and Target Identification in ONcology (ACTION), UNICANCER-UNICANCER-Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), École Pratique des Hautes Études (EPHE), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), École pratique des hautes études (EPHE)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut Bergonié - CRLCC Bordeaux, Institut Bergonié - Département de médecine, Université Bordeaux Segalen - Bordeaux 2-Centre régional de lutte contre le cancer [CRLCC], Université Bordeaux Segalen - Bordeaux 2-Institut Bergonié - CRLCC Bordeaux-Institut National de la Santé et de la Recherche Médicale (INSERM)
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Nature
Nature, Nature Publishing Group, 2020, 577 (7791), pp.556-560. ⟨10.1038/s41586-019-1906-8⟩
Nature, 2020, 577 (7791), pp.556-560. ⟨10.1038/s41586-019-1906-8⟩
ISSN: 0028-0836
1476-4679
1476-4687
DOI: 10.1038/s41586-019-1906-8⟩
Popis: Soft-tissue sarcomas represent a heterogeneous group of cancer, with more than 50 histological subtypes1,2. The clinical presentation of patients with different subtypes is often atypical, and responses to therapies such as immune checkpoint blockade vary widely3,4. To explain this clinical variability, here we study gene expression profiles in 608 tumours across subtypes of soft-tissue sarcoma. We establish an immune-based classification on the basis of the composition of the tumour microenvironment and identify five distinct phenotypes: immune-low (A and B), immune-high (D and E), and highly vascularized (C) groups. In situ analysis of an independent validation cohort shows that class E was characterized by the presence of tertiary lymphoid structures that contain T cells and follicular dendritic cells and are particularly rich in B cells. B cells are the strongest prognostic factor even in the context of high or low CD8+ T cells and cytotoxic contents. The class-E group demonstrated improved survival and a high response rate to PD1 blockade with pembrolizumab in a phase 2 clinical trial. Together, this work confirms the immune subtypes in patients with soft-tissue sarcoma, and unravels the potential of B-cell-rich tertiary lymphoid structures to guide clinical decision-making and treatments, which could have broader applications in other diseases. Immune profiling of the tumour microenvironment of soft-tissue sarcoma identifies a group of patients with high levels of B-cell infiltration and tertiary lymphoid structures that have improved survival and a high response rate to immune checkpoint blockade therapy.
Databáze: OpenAIRE
Externí odkaz: