B cells are associated with survival and immunotherapy response in sarcoma

Florent Petitprez, Aurélien Reyniès, Emily Z. Keung, Tom Wei-Wu Chen, Cheng-Ming Sun, Julien Calderaro, Yung-Ming Jeng, Li-Ping Hsiao, Laetitia Lacroix, Antoine Bougoüin, Marco Moreira, Guillaume Lacroix, Ivo Natario, Julien Adam, Carlo Lucchesi, Yec′han Laizet, Maud Toulmonde, Melissa A. Burgess, Vanessa Bolejack, Denise Reinke, Khalid M. Wani, Wei-Lien Wang, Alexander J. Lazar, Christina L. Roland, Jennifer A. Wargo, Antoine Italiano, Catherine Sautès-Fridman, Hussein A. Tawbi () and Wolf H. Fridman ()
Additional contact information
Florent Petitprez: Centre de Recherche des Cordeliers, INSERM
Aurélien Reyniès: Ligue Nationale Contre le Cancer
Emily Z. Keung: The University of Texas MD Anderson Cancer Center
Tom Wei-Wu Chen: National Taiwan University College of Medicine
Cheng-Ming Sun: Centre de Recherche des Cordeliers, INSERM
Julien Calderaro: Centre de Recherche des Cordeliers, INSERM
Yung-Ming Jeng: National Taiwan University
Li-Ping Hsiao: National Taiwan University Hospital
Laetitia Lacroix: Centre de Recherche des Cordeliers, INSERM
Antoine Bougoüin: Centre de Recherche des Cordeliers, INSERM
Marco Moreira: Centre de Recherche des Cordeliers, INSERM
Guillaume Lacroix: Centre de Recherche des Cordeliers, INSERM
Ivo Natario: Centre de Recherche des Cordeliers, INSERM
Julien Adam: Department of Biology and Pathology, Gustave Roussy
Carlo Lucchesi: Institut Bergonié
Yec′han Laizet: Institut Bergonié
Maud Toulmonde: Institut Bergonié
Melissa A. Burgess: University of Pittsburgh
Vanessa Bolejack: Cancer Research and Biostatistics
Denise Reinke: Sarcoma Alliance for Research Through Collaboration
Khalid M. Wani: The University of Texas MD Anderson Cancer Center
Wei-Lien Wang: The University of Texas MD Anderson Cancer Center
Alexander J. Lazar: The University of Texas MD Anderson Cancer Center
Christina L. Roland: The University of Texas MD Anderson Cancer Center
Jennifer A. Wargo: The University of Texas MD Anderson Cancer Center
Antoine Italiano: Institut Bergonié
Catherine Sautès-Fridman: Centre de Recherche des Cordeliers, INSERM
Hussein A. Tawbi: The University of Texas MD Anderson Cancer Center
Wolf H. Fridman: Centre de Recherche des Cordeliers, INSERM

Nature, 2020, vol. 577, issue 7791, 556-560

Abstract: Abstract 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.

Date: 2020
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DOI: 10.1038/s41586-019-1906-8

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