美国德克萨斯大学MD安德森癌症中心Jennifer A. Wargo和Beth A. Helmink团队合作，发现B细胞和三级淋巴样结构促进免疫治疗反应。2020年1月15日，国际知名学术期刊《自然》在线发表了这一成果。

他们进行了批量RNA测序，发现B细胞标志物是应答者和非应答者肿瘤中表达水平区别最大的基因。他们的发现被计算方法-MCP-counter证实，以评估该研究小组和另外两个接受免疫检查点封锁（ICB）治疗的群体（黑色素瘤和肾细胞癌患者）的免疫和基质组成。组织学评估突出了三级淋巴结构内B细胞的定位。他们通过批量和单细胞RNA测序评估了B细胞的潜在功能性贡献，这证明了B细胞在响应者中的克隆扩增和独特功能状态。大量细胞计数表明，转换记忆B细胞富含应答者的肿瘤。总之，这些数据提供了对B细胞和三级淋巴结构在ICB治疗反应中潜在作用的见解，对生物标志物和治疗靶标的开发有影响。

据悉， ICB的治疗彻底改变了癌症治疗方法。迄今为止，预测性生物标志物和增强临床反应的策略主要集中在T细胞区室。但是，其他免疫亚群也可能有助于抗肿瘤免疫，尽管在ICB治疗中研究较少。先前在黑色素瘤患者中进行的新辅助ICB试验通过靶向表达谱分析显示，对治疗有反应的患者和无反应的患者的肿瘤中富含B细胞标志。

附：英文原文

Title: B cells and tertiary lymphoid structures promote immunotherapy response

Author: Beth A. Helmink, Sangeetha M. Reddy, Jianjun Gao, Shaojun Zhang, Rafet Basar, Rohit Thakur, Keren Yizhak, Moshe Sade-Feldman, Jorge Blando, Guangchun Han, Vancheswaran Gopalakrishnan, Yuanxin Xi, Hao Zhao, Rodabe N. Amaria, Hussein A. Tawbi, Alex P. Cogdill, Wenbin Liu, Valerie S. LeBleu, Fernanda G. Kugeratski, Sapna Patel, Michael A. Davies, Patrick Hwu, Jeffrey E. Lee, Jeffrey E. Gershenwald, Anthony Lucci, Reetakshi Arora, Scott Woodman, Emily Z. Keung, Pierre-Olivier Gaudreau, Alexandre Reuben, Christine N. Spencer, Elizabeth M. Burton, Lauren E. Haydu, Alexander J. Lazar, Roberta Zapassodi, Courtney W. Hudgens, Deborah A. Ledesma, SuFey Ong, Michael Bailey, Sarah Warren, Disha Rao, Oscar Krijgsman, Elisa A. Rozeman, Daniel Peeper, Christian U. Blank, Ton N. Schumacher, Lisa H. Butterfield, Monika A. Zelazowska, Kevin M. McBride, Raghu Kalluri, James Allison, Florent Petitprez, Wolf Herman Fridman, Catherine Sauts-Fridman, Nir Hacohen, Katayoun Rezvani, Padmanee Sharma, Michael T. Tetzlaff, Linghua Wang, Jennifer A. Wargo

Issue&Volume: 2020-01-15

Abstract: Treatment with immune checkpoint blockade (ICB) has revolutionized cancer therapy. Until now, predictive biomarkers1,2,3,4,5,6,7,8,9,10 and strategies to augment clinical response have largely focused on the T cell compartment. However, other immune subsets may also contribute to anti-tumour immunity11,12,13,14,15, although these have been less well-studied in ICB treatment16. A previously conducted neoadjuvant ICB trial in patients with melanoma showed via targeted expression profiling17 that B cell signatures were enriched in the tumours of patients who respond to treatment versus non-responding patients. To build on this, here we performed bulk RNA sequencing and found that B cell markers were the most differentially expressed genes in the tumours of responders versus non-responders. Our findings were corroborated using a computational method (MCP-counter18) to estimate the immune and stromal composition in this and two other ICB-treated cohorts (patients with melanoma and renal cell carcinoma). Histological evaluation highlighted the localization of B cells within tertiary lymphoid structures. We assessed the potential functional contributions of B cells via bulk and single-cell RNA sequencing, which demonstrate clonal expansion and unique functional states of B cells in responders. Mass cytometry showed that switched memory B cells were enriched in the tumours of responders. Together, these data provide insights into the potential role of B cells and tertiary lymphoid structures in the response to ICB treatment, with implications for the development of biomarkers and therapeutic targets.

DOI: 10.1038/s41586-019-1922-8

Source: https://www.nature.com/articles/s41586-019-1922-8