Daniel H. Shu, Won Jin Ho, Luciane T. Kagohara, Alexander Girgis, Sarah M. Shin, Ludmila Danilova, Jae W. Lee, Dimitrios N. Sidiropoulos, Sarah Mitchell, Kabeer Munjal, Kathryn Howe, Kayla J. Bendinelli, Emma Kartalia, Hanfei Qi, Guanglan Mo, Janelle Montagne, James M. Leatherman, Tamara Y. Lopez-Vidal, Qingfeng Zhu, Amanda L. Huff, Xuan Yuan, Alexei Hernandez, Erin M. Coyne, Neeha Zaidi, Daniel J. Zabransky, Logan L. Engle, Aleksandra Ogurtsova, Marina Baretti, Daniel Laheru, Jennifer N. Durham, Hao Wang, Joel C. Sunshine, Robert J. Johnston, Julie Stein Deutsch, Janis M. Taube, Robert A. Anders, Elizabeth M. Jaffee, Elana J. Fertig, Mark Yarchoan
{"title":"Immunotherapy response induces divergent tertiary lymphoid structure morphologies in hepatocellular carcinoma","authors":"Daniel H. Shu, Won Jin Ho, Luciane T. Kagohara, Alexander Girgis, Sarah M. Shin, Ludmila Danilova, Jae W. Lee, Dimitrios N. Sidiropoulos, Sarah Mitchell, Kabeer Munjal, Kathryn Howe, Kayla J. Bendinelli, Emma Kartalia, Hanfei Qi, Guanglan Mo, Janelle Montagne, James M. Leatherman, Tamara Y. Lopez-Vidal, Qingfeng Zhu, Amanda L. Huff, Xuan Yuan, Alexei Hernandez, Erin M. Coyne, Neeha Zaidi, Daniel J. Zabransky, Logan L. Engle, Aleksandra Ogurtsova, Marina Baretti, Daniel Laheru, Jennifer N. Durham, Hao Wang, Joel C. Sunshine, Robert J. Johnston, Julie Stein Deutsch, Janis M. Taube, Robert A. Anders, Elizabeth M. Jaffee, Elana J. Fertig, Mark Yarchoan","doi":"10.1038/s41590-024-01992-w","DOIUrl":null,"url":null,"abstract":"Tertiary lymphoid structures (TLS) are associated with improved response in solid tumors treated with immune checkpoint blockade, but understanding of the prognostic and predictive value of TLS and the circumstances of their resolution is incomplete. Here we show that in hepatocellular carcinoma treated with neoadjuvant immunotherapy, high intratumoral TLS density at the time of surgery is associated with pathologic response and improved relapse-free survival. In areas of tumor regression, we identify a noncanonical involuted morphology of TLS marked by dispersion of the B cell follicle, persistence of a T cell zone enriched for T cell–mature dendritic cell interactions and increased expression of T cell memory markers. Collectively, these data suggest that TLS can serve as both a prognostic and predictive marker of response to immunotherapy in hepatocellular carcinoma and that late-stage TLS may support T cell memory formation after elimination of a viable tumor. Here the authors functionally characterize hepatocellular carcinoma associated tertiary lymphoid structures (TLS) in patients treated with neoadjuvant immunotherapy and present further evidence for using these TLS as a biomarker of response to therapy.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"25 11","pages":"2110-2123"},"PeriodicalIF":27.7000,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nature Immunology","FirstCategoryId":"3","ListUrlMain":"https://www.nature.com/articles/s41590-024-01992-w","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Tertiary lymphoid structures (TLS) are associated with improved response in solid tumors treated with immune checkpoint blockade, but understanding of the prognostic and predictive value of TLS and the circumstances of their resolution is incomplete. Here we show that in hepatocellular carcinoma treated with neoadjuvant immunotherapy, high intratumoral TLS density at the time of surgery is associated with pathologic response and improved relapse-free survival. In areas of tumor regression, we identify a noncanonical involuted morphology of TLS marked by dispersion of the B cell follicle, persistence of a T cell zone enriched for T cell–mature dendritic cell interactions and increased expression of T cell memory markers. Collectively, these data suggest that TLS can serve as both a prognostic and predictive marker of response to immunotherapy in hepatocellular carcinoma and that late-stage TLS may support T cell memory formation after elimination of a viable tumor. Here the authors functionally characterize hepatocellular carcinoma associated tertiary lymphoid structures (TLS) in patients treated with neoadjuvant immunotherapy and present further evidence for using these TLS as a biomarker of response to therapy.
三级淋巴结构(TLS)与接受免疫检查点阻断治疗的实体瘤的反应改善有关,但人们对TLS的预后和预测价值及其解决情况的了解并不全面。在这里,我们发现在接受新辅助免疫疗法治疗的肝细胞癌中,手术时瘤内TLS密度高与病理反应和无复发生存率改善有关。在肿瘤消退区,我们发现 TLS 的非典型内卷形态,其特点是 B 细胞滤泡分散、T 细胞区持续存在,富含 T 细胞与成熟树突状细胞的相互作用,以及 T 细胞记忆标记物的表达增加。总之,这些数据表明,TLS 可作为肝细胞癌免疫疗法反应的预后和预测标志物,晚期 TLS 可在消除存活肿瘤后支持 T 细胞记忆的形成。
期刊介绍:
Nature Immunology is a monthly journal that publishes the highest quality research in all areas of immunology. The editorial decisions are made by a team of full-time professional editors. The journal prioritizes work that provides translational and/or fundamental insight into the workings of the immune system. It covers a wide range of topics including innate immunity and inflammation, development, immune receptors, signaling and apoptosis, antigen presentation, gene regulation and recombination, cellular and systemic immunity, vaccines, immune tolerance, autoimmunity, tumor immunology, and microbial immunopathology. In addition to publishing significant original research, Nature Immunology also includes comments, News and Views, research highlights, matters arising from readers, and reviews of the literature. The journal serves as a major conduit of top-quality information for the immunology community.