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B cells are associated with survival and immunotherapy response in sarcoma

Author

Listed:
  • Florent Petitprez

    (Centre de Recherche des Cordeliers, INSERM
    Université de Paris, Sorbonne Paris Cite
    Sorbonne University
    Ligue Nationale Contre le Cancer)

  • 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
    National Taiwan University Hospital
    National Taiwan University Cancer Center
    National Taiwan University)

  • Cheng-Ming Sun

    (Centre de Recherche des Cordeliers, INSERM
    Université de Paris, Sorbonne Paris Cite
    Sorbonne University)

  • Julien Calderaro

    (Centre de Recherche des Cordeliers, INSERM
    Groupe Hospitalier Henri Mondor
    Institut Mondor de Recherche Biomédicale)

  • Yung-Ming Jeng

    (National Taiwan University
    National Taiwan University)

  • Li-Ping Hsiao

    (National Taiwan University Hospital)

  • Laetitia Lacroix

    (Centre de Recherche des Cordeliers, INSERM
    Université de Paris, Sorbonne Paris Cite
    Sorbonne University)

  • Antoine Bougoüin

    (Centre de Recherche des Cordeliers, INSERM
    Université de Paris, Sorbonne Paris Cite
    Sorbonne University)

  • Marco Moreira

    (Centre de Recherche des Cordeliers, INSERM
    Université de Paris, Sorbonne Paris Cite
    Sorbonne University)

  • Guillaume Lacroix

    (Centre de Recherche des Cordeliers, INSERM
    Université de Paris, Sorbonne Paris Cite
    Sorbonne University)

  • Ivo Natario

    (Centre de Recherche des Cordeliers, INSERM
    Université de Paris, Sorbonne Paris Cite
    Sorbonne University)

  • Julien Adam

    (Department of Biology and Pathology, Gustave Roussy)

  • Carlo Lucchesi

    (Institut Bergonié
    Institut Bergonié)

  • Yec′han Laizet

    (Institut Bergonié
    Institut Bergonié)

  • Maud Toulmonde

    (Institut Bergonié
    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
    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
    The University of Texas MD Anderson Cancer Center)

  • Antoine Italiano

    (Institut Bergonié
    Institut Bergonié
    University of Bordeaux)

  • Catherine Sautès-Fridman

    (Centre de Recherche des Cordeliers, INSERM
    Université de Paris, Sorbonne Paris Cite
    Sorbonne University)

  • Hussein A. Tawbi

    (The University of Texas MD Anderson Cancer Center)

  • Wolf H. Fridman

    (Centre de Recherche des Cordeliers, INSERM
    Université de Paris, Sorbonne Paris Cite
    Sorbonne University)

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.

Suggested Citation

  • 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 & Gui, 2020. "B cells are associated with survival and immunotherapy response in sarcoma," Nature, Nature, vol. 577(7791), pages 556-560, January.
  • Handle: RePEc:nat:nature:v:577:y:2020:i:7791:d:10.1038_s41586-019-1906-8
    DOI: 10.1038/s41586-019-1906-8
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    2. Li Yuan & Guo-Dong Jia & Xiao-Fei Lv & Si-Yi Xie & Shan-Shan Guo & Da-Feng Lin & Li-Ting Liu & Dong-Hua Luo & Yi-Fu Li & Shen-Wen Deng & Ling Guo & Mu-Sheng Zeng & Xiu-Yu Cai & Sai-Lan Liu & Xue-Song , 2023. "Camrelizumab combined with apatinib in patients with first-line platinum-resistant or PD-1 inhibitor resistant recurrent/metastatic nasopharyngeal carcinoma: a single-arm, phase 2 trial," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    3. Jianming Xu & Yi Li & Qingxia Fan & Yongqian Shu & Lei Yang & Tongjian Cui & Kangsheng Gu & Min Tao & Xiuwen Wang & Chengxu Cui & Nong Xu & Juxiang Xiao & Quanli Gao & Yunpeng Liu & Tao Zhang & Yuxian, 2022. "Clinical and biomarker analyses of sintilimab versus chemotherapy as second-line therapy for advanced or metastatic esophageal squamous cell carcinoma: a randomized, open-label phase 2 study (ORIENT-2," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
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    5. Zhenzhen Xun & Xinyu Ding & Yao Zhang & Benyan Zhang & Shujing Lai & Duowu Zou & Junke Zheng & Guoqiang Chen & Bing Su & Leng Han & Youqiong Ye, 2023. "Reconstruction of the tumor spatial microenvironment along the malignant-boundary-nonmalignant axis," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
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    7. Shaoshuai Tang & Yunzhi Wang & Rongkui Luo & Rundong Fang & Yufeng Liu & Hang Xiang & Peng Ran & Yexin Tong & Mingjun Sun & Subei Tan & Wen Huang & Jie Huang & Jiacheng Lv & Ning Xu & Zhenmei Yao & Qi, 2024. "Proteomic characterization identifies clinically relevant subgroups of soft tissue sarcoma," Nature Communications, Nature, vol. 15(1), pages 1-24, December.
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    12. Nadège Gruel & Chloé Quignot & Laëtitia Lesage & Sophie El Zein & Sylvie Bonvalot & Dimitri Tzanis & Khadija Ait Rais & Fabien Quinquis & Bastien Manciot & Julien Vibert & Nadine El Tannir & Ahmed Dah, 2024. "Cellular origin and clonal evolution of human dedifferentiated liposarcoma," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
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    15. Hee Jin Cho & Kum-Hee Yun & Su-Jin Shin & Young Han Lee & Seung Hyun Kim & Wooyeol Baek & Yoon Dae Han & Sang Kyum Kim & Hyang Joo Ryu & Joohee Lee & Iksung Cho & Heounjeong Go & Jiwon Ko & Inkyung Ju, 2024. "Durvalumab plus pazopanib combination in patients with advanced soft tissue sarcomas: a phase II trial," Nature Communications, Nature, vol. 15(1), pages 1-10, December.
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    21. Marina Baretti & Ludmila Danilova & Jennifer N. Durham & Courtney B. Betts & Leslie Cope & Dimitrios N. Sidiropoulos & Joseph A. Tandurella & Soren Charmsaz & Nicole Gross & Alexei Hernandez & Won Jin, 2024. "Entinostat in combination with nivolumab in metastatic pancreatic ductal adenocarcinoma: a phase 2 clinical trial," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
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