Open AccessB cells are associated with survival and immunotherapy response in sarcoma
Author(s) -
Florent Petitprez,
Aurélien de Reyniès,
Emily Z. Keung,
Tom WeiWu Chen,
Chengming Sun,
Julien Caldéraro,
YungMing Jeng,
Li-Ping Hsiao,
Laetitia Lacroix,
Antoine Bougoüin,
Marco Moreira,
Guillaume Lacroix,
Ivo Natario,
Julien Adam,
Carlo Lucchesi,
Yec’han Laizet,
Maud Toulmonde,
Melissa Burgess,
Vanessa Bolejack,
Denise K. Reinke,
Khalid M. Wani,
WeiLien Wang,
Alexander J. Lazar,
Christina L. Roland,
Jennifer A. Wargo,
Antoîne Italiano,
Wolf–Herman Fridman,
Hussein A. Tawbi,
Wolf Herman Fridman
Publication year - 2020
Publication title -
nature
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 15.993
H-Index - 1226
eISSN - 1476-4687
pISSN - 0028-0836
DOI - 10.1038/s41586-019-1906-8
Subject(s) - pembrolizumab , immune system , cd8 , sarcoma , context (archaeology) , soft tissue sarcoma , cytotoxic t cell , immunotherapy , biology , tumor microenvironment , immune checkpoint , immunology , cancer research , medicine , pathology , in vitro , genetics , paleontology
Soft-tissue sarcomas represent a heterogeneous group of cancer, with more than 50 histological subtypes 1,2 . The clinical presentation of patients with different subtypes is often atypical, and responses to therapies such as immune checkpoint blockade vary widely 3,4 . 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.