小柯机器人

瑞典隆德大学Göran Jönsson研究组的一项最新研究表明，三级淋巴结构可改善黑色素瘤的免疫治疗和生存率。这一研究成果2020年1月15日在线发表在国际学术期刊《自然》上。

研究人员使用转移性黑色素瘤的临床样本来研究B细胞在抗肿瘤反应中的作用，并发现与肿瘤相关的CD8⁺T细胞和CD20⁺B细胞的共存与存活率提高相关，而与其他临床变量无关。CXCR5和CXCL13与CD20结合的免疫荧光染色揭示了在这些CD8⁺CD20⁺肿瘤中三级淋巴结构的形成。研究人员获得了与三级淋巴样结构相关的基因特征，其可预测接受免疫检查点封锁治疗的患者的临床结果。此外，富含B细胞的肿瘤伴有TCF7⁺初始和/或记忆T细胞水平升高。数字空间分析数据证实了这一点，其中没有三级淋巴结构肿瘤中的T细胞具有功能异常的分子表型。这些结果表明，通过赋予不同的T细胞表型，三级淋巴结构在黑色素瘤的免疫微环境中具有关键作用。以后的研究应该探讨诱导三级淋巴样结构形成的治疗策略，从而改善对癌症免疫疗法的反应。

据了解，重新激活肿瘤相关T细胞的检查点封锁疗法可以诱导持久的肿瘤控制，并促进晚期癌症患者的长期生存。当前用于治疗反应的预测性生物标志物包括高水平的肿瘤内免疫活性、高的肿瘤突变负担和肠道菌群的特殊特征。尽管已经充分研究了T细胞在抗肿瘤反应中的作用，但仍未充分探索其他免疫细胞。

附：英文原文

Title: Tertiary lymphoid structures improve immunotherapy and survival in melanoma

Author: Rita Cabrita, Martin Lauss, Adriana Sanna, Marco Donia, Mathilde Skaarup Larsen, Shamik Mitra, Iva Johansson, Bengt Phung, Katja Harbst, Johan Vallon-Christersson, Alison van Schoiack, Kristina Lvgren, Sarah Warren, Karin Jirstrm, Hkan Olsson, Kristian Pietras, Christian Ingvar, Karolin Isaksson, Dirk Schadendorf, Henrik Schmidt, Lars Bastholt, Ana Carneiro, Jennifer A. Wargo, Inge Marie Svane, Gran Jnsson

Issue&Volume: 2020-01-15

Abstract: Checkpoint blockade therapies that reactivate tumour-associated T cells can induce durable tumour control and result in the long-term survival of patients with advanced cancers1. Current predictive biomarkers for therapy response include high levels of intratumour immunological activity, a high tumour mutational burden and specific characteristics of the gut microbiota2,3. Although the role of T cells in antitumour responses has thoroughly been studied, other immune cells remain insufficiently explored. Here we use clinical samples of metastatic melanomas to investigate the role of B cells in antitumour responses, and find that the co-occurrence of tumour-associated CD8+ T cells and CD20+ B cells is associated with improved survival, independently of other clinical variables. Immunofluorescence staining of CXCR5 and CXCL13 in combination with CD20 reveals the formation of tertiary lymphoid structures in these CD8+CD20+ tumours. We derived a gene signature associated with tertiary lymphoid structures, which predicted clinical outcomes in cohorts of patients treated with immune checkpoint blockade. Furthermore, B-cell-rich tumours were accompanied by increased levels of TCF7+ naive and/or memory T cells. This was corroborated by digital spatial-profiling data, in which T cells in tumours without tertiary lymphoid structures had a dysfunctional molecular phenotype. Our results indicate that tertiary lymphoid structures have a key role in the immune microenvironment in melanoma, by conferring distinct T cell phenotypes. Therapeutic strategies to induce the formation of tertiary lymphoid structures should be explored to improve responses to cancer immunotherapy.

DOI: 10.1038/s41586-019-1914-8

Source: https://www.nature.com/articles/s41586-019-1914-8

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