Ali N Kamali, Haleh Hamedifar, Michael Eisenhut, Jose M Bautista
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引用次数: 0
摘要
多发性骨髓瘤(MM)是一种骨髓癌,在西方国家被列为第二大最常见的成人血液恶性肿瘤。尽管癌症领域的免疫疗法有了长足的进步,但多发性骨髓瘤的免疫疗法直到现在仍不被看好。最近进行的免疫检查点抑制剂疗法(无论是单独使用还是与抗癌药物联合使用)临床研究显示,该疗法副作用过大或疗效不佳,尤其是在晚期 MM 患者中。在这种情况下,淋巴细胞衰竭标志物水平在 MM 肿瘤微环境(TME)中起着举足轻重的作用。因此,本综述将讨论五种抑制分子与 MM 的相关机制,包括具有 Ig 和 ITIM 结构域的 T 细胞免疫受体(TIGIT)、T 细胞免疫球蛋白和粘蛋白结构域 3(Tim-3)、淋巴细胞活化基因-3(LAG-3)、V-结构域 Ig T 细胞活化抑制因子和杀伤性免疫球蛋白样受体以及双特异性 T 细胞抗体(BsAbs)。此外,我们还总结了这些检查点在癌症中的基本生物学特性,以及它们在 MM 中迅速崛起的作用,并介绍了最近的临床试验。
Multiple myeloma and the potential of new checkpoint inhibitors for immunotherapy.
Multiple myeloma (MM), a cancer of the bone marrow, is categorized as the second most common hematological malignancy of adults in the Western world. Despite dramatic improvements in immunotherapies in the field of cancers, MM immunotherapy has not been promising until now. Recent clinical studies of immune checkpoint inhibitor therapy, either alone or in combination with anticancer drugs, showed excessive side effects or low efficacy, particularly in advanced MM patients. In this context, lymphocyte levels of exhaustion markers play a pivotal role in the MM tumor microenvironment (TME). Hence in the present review, the mechanisms relevant to MM of five inhibitory molecules including T-cell immunoreceptor with Ig and ITIM domains (TIGIT), T-cell immunoglobulin, and mucin domain 3 (Tim-3), lymphocyte activation gene-3 (LAG-3), V-domain Ig Suppressor of T-cell activation and killer immunoglobulin-like receptors along with bispecific T-cell antibodies (BsAbs) will be discussed. Further, we summarized the underlying biology of these checkpoints in cancer and their rapidly emerging role in pathways in MM along with presenting recent clinical trials in context.