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B cells and tertiary lymphoid structures as determinants of tumour immune contexture and clinical outcome
Nature Reviews Clinical Oncology ( IF 81.1 ) Pub Date : 2022-04-01 , DOI: 10.1038/s41571-022-00619-z
Wolf H Fridman 1, 2 , Maxime Meylan 1, 2 , Florent Petitprez 3 , Cheng-Ming Sun 1, 2 , Antoine Italiano 4, 5 , Catherine Sautès-Fridman 1, 2
Affiliation  

B cells are a major component of the tumour microenvironment, where they are predominantly associated with tertiary lymphoid structures (TLS). In germinal centres within mature TLS, B cell clones are selectively activated and amplified, and undergo antibody class switching and somatic hypermutation. Subsequently, these B cell clones differentiate into plasma cells that can produce IgG or IgA antibodies targeting tumour-associated antigens. In tumours without mature TLS, B cells are either scarce or differentiate into regulatory cells that produce immunosuppressive cytokines. Indeed, different tumours vary considerably in their TLS and B cell content. Notably, tumours with mature TLS, a high density of B cells and plasma cells, as well as the presence of antibodies to tumour-associated antigens are typically associated with favourable clinical outcomes and responses to immunotherapy compared with those lacking these characteristics. However, polyclonal B cell activation can also result in the formation of immune complexes that trigger the production of pro-inflammatory cytokines by macrophages and neutrophils. In complement-rich tumours, IgG antibodies can also activate the complement cascade, resulting in the production of anaphylatoxins that sustain tumour-promoting inflammation and angiogenesis. Herein, we review the phenotypic heterogeneity of intratumoural B cells and the importance of TLS in their generation as well as the potential of B cells and TLS as prognostic and predictive biomarkers. We also discuss novel therapeutic approaches that are being explored with the aim of increasing mature TLS formation, B cell differentiation and anti-tumour antibody production within tumours.



中文翻译:

B细胞和三级淋巴结构作为肿瘤免疫环境和临床结果的决定因素

B 细胞是肿瘤微环境的主要组成部分,它们主要与三级淋巴结构 (TLS) 相关。在成熟 TLS 的生发中心,B 细胞克隆被选择性激活和扩增,并经历抗体类别转换和体细胞超突变。随后,这些 B 细胞克隆分化成浆细胞,可产生靶向肿瘤相关抗原的 IgG 或 IgA 抗体。在没有成熟 TLS 的肿瘤中,B 细胞要么稀少,要么分化为产生免疫抑制细胞因子的调节细胞。事实上,不同肿瘤的 TLS 和 B 细胞含量差异很大。值得注意的是,具有成熟 TLS、高密度 B 细胞和浆细胞的肿瘤,与缺乏这些特征的患者相比,肿瘤相关抗原抗体的存在通常与有利的临床结果和对免疫疗法的反应有关。然而,多克隆 B 细胞激活也可导致免疫复合物的形成,从而触发巨噬细胞和中性粒细胞产生促炎细胞因子。在富含补体的肿瘤中,IgG 抗体还可以激活补体级联反应,导致产生过敏毒素,从而维持促进肿瘤的炎症和血管生成。在此,我们回顾了肿瘤内 B 细胞的表型异质性和 TLS 在其生成中的重要性,以及 B 细胞和 TLS 作为预后和预测生物标志物的潜力。

更新日期:2022-04-01
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