慢性淋巴细胞白血病（CLL）是一种克隆性扩张的抗原转换、肿瘤性、成熟的B细胞恶性肿瘤。CLL特征为免疫抑制程度不同以及二次低γ球蛋白血症。B细胞去除治疗历史上已被使用，但一定比例的患者对多种治疗线路产生抵抗，并伴随免疫抑制恶化和感染风险增高。分子诊断技术的进步和新型药物的研发，如靶向Bruton酪氨酸激酶和B细胞淋巴瘤-2的药物，已经为增加感染风险并从CLL中复杂的肿瘤环境中逃脱的细胞机制提供了新的见解。一般而言，多价人免疫球蛋白G（IgG）的免疫球蛋白替代治疗适用于重复发作的严重细菌感染和低IgG水平的患者，但对于启动此类治疗的IgG水平的门槛没有共识。一定比例的CLL患者仍有残余的IgG产生，并保持了免疫球蛋白分子的质量，因此，“IgG质量”的定义可能让这些患者采用更低剂量或更少次数的免疫球蛋白治疗。免疫球蛋白治疗可以恢复先天免疫力，并且与CLL靶向治疗结合使用，可以使T细胞抗原初级，恢复T细胞功能，从而提供可能从肿瘤相关自身免疫性和免疫介导的抗肿瘤效应中逃脱的机会。本综述旨在讨论CLL靶向治疗如何通过减少肿瘤体积和恢复免疫功能与免疫球蛋白替代治疗发挥协同治疗效应的机制。版权所有©2023 Khan、Allsup和Molica。

Chronic lymphocytic leukaemia (CLL) is a malignancy of clonally expanded antigen-switched, neoplastic, mature B cells. CLL is characterised by a variable degree of immunosuppression and secondary hypogammaglobulinemia. B-cell depleting therapies have historically been deployed with a proportion of patients becoming resistant to multiple lines of treatment with an associated worsening of immunosuppression and heightened infection risk. Advances in molecular diagnostics and the development of new therapies targeting Bruton's tyrosine kinase and B-cell lymphoma-2 have resulted in novel insights into the cellular mechanisms associated with an increased infection risk and T-cell escape from the complex tumour environment found in CLL. Generally, immunoglobulin replacement therapy with polyvalent human immunoglobulin G (IgG) is indicated in patients with recurrent severe bacterial infections and low IgG levels, but there is no consensus on the threshold IgG level for initiation of such therapy. A proportion of CLL patients have residual IgG production, with preserved quality of the immunoglobulin molecules, and therefore a definition of 'IgG quality' may allow for lower dosing or less frequent treatment with immunoglobulin therapy in such patients. Immunoglobulin therapy can restore innate immunity and in conjunction with CLL targeted therapies may allow T-cell antigen priming, restore T-cell function thereby providing an escape from tumour-associated autoimmunity and the development of an immune-mediated anti-tumour effect. This review aims to discuss the mechanisms by which CLL-targeted therapy may exert a synergistic therapeutic effect with immunoglobulin replacement therapy both in terms of reducing tumour bulk and restoration of immune function.Copyright © 2023 Khan, Allsup and Molica.