实体瘤通常表现出染色体拷贝数变异，这通常是由有丝分裂中的染色体不稳定性（CIN）引起的。由此产生的非整倍性可以推动进化，并与各种癌症类型的不良预后以及黑色素瘤中对 T 细胞检查点阻断的不良反应相关。在这种情况下，巨噬细胞和 SIRPα-CD47 检查点尚未得到充分研究。在这里，使用纺锤体组装检查点 MPS1 抑制剂在免疫原性差的 B16F10 小鼠黑色素瘤细胞中诱导 CIN，该抑制剂产生持久的微核和多样化的非整倍性，同时根据标记和短期抗肿瘤研究使巨噬细胞偏向杀肿瘤“M1 样”表型。带有野生型 CD47 水平的 CIN 肿瘤小鼠的死亡情况与对照组类似，但通过对过继转移的骨髓细胞加上抗肿瘤单克隆 IgG 进行 SIRPα 阻断，可以最大限度地延长长期存活率。这些细胞是起始效应细胞，幸存者从头制造抗癌 IgG，不仅促进 CD47 缺失细胞的吞噬作用，还抑制肿瘤生长。 CIN 不会影响 IgG 反应，但将 CIN 与最大巨噬细胞抗癌活性配对可增加持久治疗效果，并具有类似疫苗接种的抗复发反应。© 2023，Hayes 等人。

Solid tumors generally exhibit chromosome copy number variation, which is typically caused by chromosomal instability (CIN) in mitosis. The resulting aneuploidy can drive evolution and associates with poor prognosis in various cancer types as well as poor response to T-cell checkpoint blockade in melanoma. Macrophages and the SIRPα-CD47 checkpoint are understudied in such contexts. Here, CIN is induced in poorly immunogenic B16F10 mouse melanoma cells using spindle assembly checkpoint MPS1 inhibitors that generate persistent micronuclei and diverse aneuploidy while skewing macrophages toward a tumoricidal 'M1-like' phenotype based on markers and short-term anti-tumor studies. Mice bearing CIN-afflicted tumors with wild-type CD47 levels succumb similar to controls, but long-term survival is maximized by SIRPα blockade on adoptively transferred myeloid cells plus anti-tumor monoclonal IgG. Such cells are the initiating effector cells, and survivors make de novo anti-cancer IgG that not only promote phagocytosis of CD47-null cells but also suppress tumor growth. CIN does not affect the IgG response, but pairing CIN with maximal macrophage anti-cancer activity increases durable cures that possess a vaccination-like response against recurrence.© 2023, Hayes et al.