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B cells are associated with survival and immunotherapy response in sarcoma.
Nature 2020; 577(7791):556-560Nat

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.

Authors+Show Affiliations

Team Cancer, Immune Control and Escape, Centre de Recherche des Cordeliers, INSERM, Paris, France. Centre de Recherche des Cordeliers, Université de Paris, Sorbonne Paris Cite, Paris, France. Centre de Recherche des Cordeliers, Sorbonne University, Paris, France. Programme Cartes d'Identité des Tumeurs, Ligue Nationale Contre le Cancer, Paris, France.Programme Cartes d'Identité des Tumeurs, Ligue Nationale Contre le Cancer, Paris, France.Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei, Taiwan. Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan. National Taiwan University Cancer Center, Taipei, Taiwan. Centers of Genomic and Precision Medicine, National Taiwan University, Taipei, Taiwan.Team Cancer, Immune Control and Escape, Centre de Recherche des Cordeliers, INSERM, Paris, France. Centre de Recherche des Cordeliers, Université de Paris, Sorbonne Paris Cite, Paris, France. Centre de Recherche des Cordeliers, Sorbonne University, Paris, France.Team Cancer, Immune Control and Escape, Centre de Recherche des Cordeliers, INSERM, Paris, France. Département de Pathologie, Assistance Publique Hôpitaux de Paris, Groupe Hospitalier Henri Mondor, Creteil, France. Institut Mondor de Recherche Biomédicale, Creteil, France.Centers of Genomic and Precision Medicine, National Taiwan University, Taipei, Taiwan. Department of Pathology, National Taiwan University, Taipei, Taiwan.Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan.Team Cancer, Immune Control and Escape, Centre de Recherche des Cordeliers, INSERM, Paris, France. Centre de Recherche des Cordeliers, Université de Paris, Sorbonne Paris Cite, Paris, France. Centre de Recherche des Cordeliers, Sorbonne University, Paris, France.Team Cancer, Immune Control and Escape, Centre de Recherche des Cordeliers, INSERM, Paris, France. Centre de Recherche des Cordeliers, Université de Paris, Sorbonne Paris Cite, Paris, France. Centre de Recherche des Cordeliers, Sorbonne University, Paris, France.Team Cancer, Immune Control and Escape, Centre de Recherche des Cordeliers, INSERM, Paris, France. Centre de Recherche des Cordeliers, Université de Paris, Sorbonne Paris Cite, Paris, France. Centre de Recherche des Cordeliers, Sorbonne University, Paris, France.Team Cancer, Immune Control and Escape, Centre de Recherche des Cordeliers, INSERM, Paris, France. Centre de Recherche des Cordeliers, Université de Paris, Sorbonne Paris Cite, Paris, France. Centre de Recherche des Cordeliers, Sorbonne University, Paris, France.Team Cancer, Immune Control and Escape, Centre de Recherche des Cordeliers, INSERM, Paris, France. Centre de Recherche des Cordeliers, Université de Paris, Sorbonne Paris Cite, Paris, France. Centre de Recherche des Cordeliers, Sorbonne University, Paris, France.Department of Biology and Pathology, Gustave Roussy, Villejuif, France.Institut Bergonié, Bordeaux, France. Bioinformatics Unit, Institut Bergonié, Bordeaux, France.Institut Bergonié, Bordeaux, France. Bioinformatics Unit, Institut Bergonié, Bordeaux, France.Institut Bergonié, Bordeaux, France. Department of Medical Oncology, Institut Bergonié, Bordeaux, France.Department of Medicine, Divison of Hematology/Oncology, University of Pittsburgh, Pittsburgh, PA, USA.Cancer Research and Biostatistics, Seattle, WA, USA.Sarcoma Alliance for Research Through Collaboration, Ann Arbor, MI, USA.Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.Institut Bergonié, Bordeaux, France. Department of Medical Oncology, Institut Bergonié, Bordeaux, France. University of Bordeaux, Bordeaux, France.Team Cancer, Immune Control and Escape, Centre de Recherche des Cordeliers, INSERM, Paris, France. Centre de Recherche des Cordeliers, Université de Paris, Sorbonne Paris Cite, Paris, France. Centre de Recherche des Cordeliers, Sorbonne University, Paris, France.Department of Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. htawbi@mdanderson.org.Team Cancer, Immune Control and Escape, Centre de Recherche des Cordeliers, INSERM, Paris, France. herve.fridman@crc.jussieu.fr. Centre de Recherche des Cordeliers, Université de Paris, Sorbonne Paris Cite, Paris, France. herve.fridman@crc.jussieu.fr. Centre de Recherche des Cordeliers, Sorbonne University, Paris, France. herve.fridman@crc.jussieu.fr.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

31942077

Citation

Petitprez, Florent, et al. "B Cells Are Associated With Survival and Immunotherapy Response in Sarcoma." Nature, vol. 577, no. 7791, 2020, pp. 556-560.
Petitprez F, de Reyniès A, Keung EZ, et al. B cells are associated with survival and immunotherapy response in sarcoma. Nature. 2020;577(7791):556-560.
Petitprez, F., de Reyniès, A., Keung, E. Z., Chen, T. W., Sun, C. M., Calderaro, J., ... Fridman, W. H. (2020). B cells are associated with survival and immunotherapy response in sarcoma. Nature, 577(7791), pp. 556-560. doi:10.1038/s41586-019-1906-8.
Petitprez F, et al. B Cells Are Associated With Survival and Immunotherapy Response in Sarcoma. Nature. 2020;577(7791):556-560. PubMed PMID: 31942077.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - B cells are associated with survival and immunotherapy response in sarcoma. AU - Petitprez,Florent, AU - de Reyniès,Aurélien, AU - Keung,Emily Z, AU - Chen,Tom Wei-Wu, AU - Sun,Cheng-Ming, AU - Calderaro,Julien, AU - Jeng,Yung-Ming, AU - Hsiao,Li-Ping, AU - Lacroix,Laetitia, AU - Bougoüin,Antoine, AU - Moreira,Marco, AU - Lacroix,Guillaume, AU - Natario,Ivo, AU - Adam,Julien, AU - Lucchesi,Carlo, AU - Laizet,Yec Han, AU - Toulmonde,Maud, AU - Burgess,Melissa A, AU - Bolejack,Vanessa, AU - Reinke,Denise, AU - Wani,Khalid M, AU - Wang,Wei-Lien, AU - Lazar,Alexander J, AU - Roland,Christina L, AU - Wargo,Jennifer A, AU - Italiano,Antoine, AU - Sautès-Fridman,Catherine, AU - Tawbi,Hussein A, AU - Fridman,Wolf H, Y1 - 2020/01/15/ PY - 2018/06/29/received PY - 2019/11/26/accepted PY - 2020/1/17/pubmed PY - 2020/1/17/medline PY - 2020/1/17/entrez SP - 556 EP - 560 JF - Nature JO - Nature VL - 577 IS - 7791 N2 - 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. SN - 1476-4687 UR - https://www.unboundmedicine.com/medline/citation/31942077/B_cells_are_associated_with_survival_and_immunotherapy_response_in_sarcoma L2 - https://doi.org/10.1038/s41586-019-1906-8 DB - PRIME DP - Unbound Medicine ER -