B cells are associated with survival and immunotherapy response in sarcoma

Florent Petitprez; Aurélien de 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; Wolf H. Fridman

doi:10.1038/s41586-019-1906-8

B cells are associated with survival and immunotherapy response in sarcoma

Florent Petitprez, Aurélien de 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 ReinkeKhalid M. Wani, Wei Lien Wang, Alexander J. Lazar, Christina L. Roland, Jennifer A. Wargo, Antoine Italiano, Catherine Sautès-Fridman, Hussein A. Tawbi, Wolf H. Fridman

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Abstract

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.

Original language	English (US)
Pages (from-to)	556-560
Number of pages	5
Journal	Nature
Volume	577
Issue number	7791
DOIs	https://doi.org/10.1038/s41586-019-1906-8
State	Published - Jan 23 2020

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Petitprez, F., de Reyniès, A., Keung, E. Z., Chen, T. W. W., Sun, C. M., Calderaro, J., Jeng, Y. M., Hsiao, L. P., Lacroix, L., Bougoüin, A., Moreira, M., Lacroix, G., Natario, I., Adam, J., Lucchesi, C., Laizet, Y., Toulmonde, M., Burgess, M. A., Bolejack, V., ... Fridman, W. H. (2020). B cells are associated with survival and immunotherapy response in sarcoma. Nature, 577(7791), 556-560. https://doi.org/10.1038/s41586-019-1906-8

Petitprez, F, de Reyniès, A, Keung, EZ, Chen, TWW, Sun, CM, Calderaro, J, Jeng, YM, Hsiao, LP, Lacroix, L, Bougoüin, A, Moreira, M, Lacroix, G, Natario, I, Adam, J, Lucchesi, C, Laizet, Y, Toulmonde, M, Burgess, MA, Bolejack, V, Reinke, D, Wani, KM, Wang, WL , Lazar, AJ , Roland, CL , Wargo, JA, Italiano, A, Sautès-Fridman, C, Tawbi, HA & Fridman, WH 2020, 'B cells are associated with survival and immunotherapy response in sarcoma', Nature, vol. 577, no. 7791, pp. 556-560. https://doi.org/10.1038/s41586-019-1906-8

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title = "B cells are associated with survival and immunotherapy response in sarcoma",

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.",

author = "Florent Petitprez and {de Reyni{\`e}s}, Aur{\'e}lien and Keung, {Emily Z.} and Chen, {Tom Wei Wu} and Sun, {Cheng Ming} and Julien Calderaro and Jeng, {Yung Ming} and Hsiao, {Li Ping} and Laetitia Lacroix and Antoine Bougo{\"u}in and Marco Moreira and Guillaume Lacroix and Ivo Natario and Julien Adam and Carlo Lucchesi and Yec′han Laizet and Maud Toulmonde and Burgess, {Melissa A.} and Vanessa Bolejack and Denise Reinke and Wani, {Khalid M.} and Wang, {Wei Lien} and Lazar, {Alexander J.} and Roland, {Christina L.} and Wargo, {Jennifer A.} and Antoine Italiano and Catherine Saut{\`e}s-Fridman and Tawbi, {Hussein A.} and Fridman, {Wolf H.}",

note = "Publisher Copyright: {\textcopyright} 2020, The Author(s), under exclusive licence to Springer Nature Limited.",

year = "2020",

month = jan,

day = "23",

doi = "10.1038/s41586-019-1906-8",

language = "English (US)",

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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.

PY - 2020/1/23

Y1 - 2020/1/23

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.

AB - 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.

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U2 - 10.1038/s41586-019-1906-8

DO - 10.1038/s41586-019-1906-8

M3 - Article

C2 - 31942077

AN - SCOPUS:85078153209

SN - 0028-0836

VL - 577

SP - 556

EP - 560

JO - Nature

JF - Nature

IS - 7791

ER -

B cells are associated with survival and immunotherapy response in sarcoma

Abstract

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