CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题：Immunomodulatory Effect of Proteasome Inhibitors via the Induction of Immunogenic Cell Death in Myeloma Cells.
Immunomodulatory Effect of Proteasome Inhibitors via the Induction of Immunogenic Cell Death in Myeloma Cells.
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已知多种抗癌药物具有免疫调节作用，包括诱导癌细胞发生免疫原性细胞死亡（ICD）。ICD是一种凋亡形式，由损伤相关分子模式（DAMPs）的释放、树突状细胞对肿瘤抗原的摄取以及针对癌细胞的获得性免疫激活所引起。ICD最初在实体瘤中被报道，而关于多发性骨髓瘤（MM）中ICD的报道较少。在此，我们发现包括卡非佐米在内的蛋白酶体抑制剂通过一条不同于实体瘤的未折叠蛋白反应通路诱导骨髓瘤细胞发生ICD。此外，我们证明了ICD对骨髓瘤患者生存的潜在影响。蛋白酶体抑制剂诱导的ICD有望不仅通过其细胞毒性作用，还可通过与其他疗法（如CAR-T 细胞疗法）联合建立针对MM细胞的强免疫记忆反应，从而改善MM患者的预后。
Several anti-cancer drugs are known to have immunomodulatory effects, including immunogenic cell death (ICD) of cancer cells. ICD is a form of apoptosis which is caused by the release of damage-associated molecular patterns (DAMPs), the uptake of cancer antigens by dendritic cells, and the activation of acquired immunity against cancer cells. ICD was originally reported in solid tumors, and there have been few reports on ICD in multiple myeloma (MM).
Here, we showed that proteasome inhibitors, including carfilzomib, induce ICD in myeloma cells via an unfolded protein response pathway distinct from that in solid tumors.
Additionally, we demonstrated the potential impact of ICD on the survival of patients with myeloma. ICD induced by proteasome inhibitors is expected to improve the prognosis of MM patients not only by its cytotoxic effects, but also by building strong immune memory response against MM cells in combination with other therapies, such as chimeric antigen receptor-T cell therapy.
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