小柯机器人

B细胞影响肉瘤患者的生存和免疫治疗
2020-01-16 16:57

2020年1月15日,法国国家健康与医学研究院Wolf H. Fridman和美国得克萨斯大学MD安德森癌症中心Hussein A. Tawbi研究组在《自然》在线发表论文。他们发现在肉瘤中,B细胞与生存和免疫治疗反应相关。

为了解释肉瘤的临床异质性,研究人员探究了软组织肉瘤亚型中608种肿瘤的基因表达谱。研究人员根据肿瘤微环境的组成建立了基于免疫学的分类,并将其分为五种不同的表型:低免疫(A和B),高免疫(D和E)和高度血管化(C)组。对独立验证队列的原位分析表明,E类的特征是存在三级淋巴样结构,该结构包含T细胞和滤泡树突状细胞,尤其是富含B细胞。即使在高或低CD8 + T细胞或细胞毒性的条件下,B细胞也是最强的影响预后的因素。一项2期临床试验表明,E组提高了对派姆单抗联合PD1阻滞疗法的应答率并且改善了生存率。总之,这项工作揭示了软组织肉瘤患者的免疫亚型,并发现富含B细胞的三级淋巴结构在指导临床决策和治疗的潜力,这在其他疾病中也可能应用价值。

据介绍,软组织肉瘤是癌症的异质性组,具有50多种组织学亚型。通常不同亚型患者的临床表现是特异的,并且对诸如免疫检查点封锁等疗法的反应也存在很大差异。

附:英文原文

Title: B cells are associated with survival and immunotherapy response in sarcoma

Author: Florent Petitprez, Aurlien de Reynis, Emily Z. Keung, Tom Wei-Wu Chen, Cheng-Ming Sun, Julien Calderaro, Yung-Ming Jeng, Li-Ping Hsiao, Laetitia Lacroix, Antoine Bougoin, Marco Moreira, Guillaume Lacroix, Ivo Natario, Julien Adam, Carlo Lucchesi, Yechan 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 Sauts-Fridman, Hussein A. Tawbi, Wolf H. Fridman

Issue&Volume: 2020-01-15

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.

DOI: 10.1038/s41586-019-1906-8

Source: https://www.nature.com/articles/s41586-019-1906-8

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:69.504
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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