Hospital Santa Creu i San Pau, Barcelona, Spain.
Hospital Universitario de la Princesa, Madrid, Spain.
J Exp Clin Cancer Res. 2021 Oct 15;40(1):321. doi: 10.1186/s13046-021-02115-1.
Chronic Lymphocytic Leukemia (CLL) is a hematological malignancy characterized by uncontrolled proliferation of B-cells and severe immune dysfunction. Chemo(immuno)therapies (CIT) have traditionally aimed to reduce tumor burden without fully understanding their effects on the immune system. As a consequence, CIT are usually associated with higher risk of infections, secondary neoplasms and autoimmune disorders. A better understanding of the biology of the disease has led to the development of therapeutic strategies which not only act against malignant B-cells but also reactivate and enhance the patient's own anti-tumor immune response. Here, we review the current understanding of the underlying interplay between the malignant cells and non-malignant immune cells that may promote tumor survival and proliferation. In addition, we review the available evidence on how different treatment options for CLL including CIT regimens, small molecular inhibitors (i.e, BTK inhibitors, PI3K inhibitors, BCL-2 inhibitors) and T-cell therapies, affect the immune system and their clinical consequences. Finally, we propose that a dual therapeutic approach, acting directly against malignant B-cells and restoring the immune function is clinically relevant and should be considered when developing future strategies to treat patients with CLL.
慢性淋巴细胞白血病（CLL）是一种血液系统恶性肿瘤，其特征是 B 细胞不受控制地增殖和严重的免疫功能障碍。化疗（免疫）疗法（CIT）传统上旨在减轻肿瘤负担，但不完全了解其对免疫系统的影响。因此，CIT 通常与更高的感染风险、继发性肿瘤和自身免疫性疾病相关。对疾病生物学的更好理解导致了治疗策略的发展，这些策略不仅针对恶性 B 细胞，而且还能重新激活和增强患者自身的抗肿瘤免疫反应。在这里，我们回顾了恶性细胞和非恶性免疫细胞之间潜在相互作用的最新认识，这些相互作用可能促进肿瘤的存活和增殖。此外，我们还回顾了关于不同的 CLL 治疗选择（包括 CIT 方案、小分子抑制剂（即 BTK 抑制剂、PI3K 抑制剂、BCL-2 抑制剂）和 T 细胞疗法）如何影响免疫系统及其临床后果的现有证据。最后，我们提出，直接针对恶性 B 细胞并恢复免疫功能的双重治疗方法具有临床相关性，在制定治疗 CLL 患者的未来策略时应予以考虑。
