Targeted therapy of cancer typically focuses on inhibitors (for example, tyrosine kinase inhibitors) that suppress oncogenic signalling below a minimum threshold required for survival and proliferation of cancer cells. B cell acute lymphoblastic leukaemia and B cell lymphomas originate from various stages of development of B cells, which, unlike other cell types, are under intense selective pressure. The vast majority of newly generated B cells are autoreactive and die by negative selection at autoimmunity checkpoints (AICs). Owing to ubiquitous encounters with self-antigen, autoreactive B cells are eliminated by the overwhelming signalling strength of their autoreactive B cell receptor (BCR). A series of recent findings suggests that, despite malignant transformation, AICs are fully functional in B cell malignancies. This Opinion article proposes targeted engagement of AICs as a previously unrecognized therapeutic opportunity to overcome drug resistance in B cell malignancies.

癌症的靶向治疗通常集中在抑制剂（例如酪氨酸激酶抑制剂）上，该抑制剂将致癌信号抑制在癌细胞存活和增殖所需的最小阈值以下。B细胞急性淋巴细胞白血病和B细胞淋巴瘤起源于B细胞发育的各个阶段，与其他细胞类型不同，B细胞处于强烈的选择压力下。绝大多数新产生的B细胞是自身反应性的，并在自身免疫检查点（AIC）处因阴性选择而死亡。由于自身抗原的普遍存在，自身反应性B细胞通过其自身反应性B细胞受体（BCR）的压倒性信号强度而被消除。一系列最新发现表明，尽管发生了恶性转化，AIC在B细胞恶性肿瘤中仍具有完整的功能。