肿瘤细胞治疗研究
英文原题：Present and Future Role of Immune Targets in Acute Myeloid Leukemia.
目前众所周知，骨髓（BM）细胞龛参与白血病发生，但新出现的证据支持AML细胞与BM微环境之间复杂的交互作用在诱导允许性免疫环境中的作用，该环境保护白血病干细胞（LSCs）免受治疗诱导的死亡，从而有利于疾病持续和最终复发。
目前已明确，骨髓（BM）细胞生态位参与白血病发生。新兴证据进一步表明，AML细胞与BM微环境之间复杂的相互作用可形成有利的免疫环境，使白血病干细胞（LSC）免于治疗诱导的死亡，从而促进疾病持续存在和最终复发。鉴定AML细胞上的潜在免疫靶点并调节BM微环境，可能增强药物抗白血病作用、重新激活免疫系统并恢复对白血病的免疫监视。此类免疫治疗的潜在靶点和效应手段包括：靶向CD33、CD123和CLL-1等LSC抗原的单克隆抗体（可直接靶向，或构建双特异性T细胞衔接器）；单独或联合传统AML药物、作用于不同共抑制轴的免疫检查点抑制剂；以及靶向AML特异性抗原的新型细胞疗法，例如嵌合抗原受体（CAR）T细胞。尽管全球正在开展数十项临床试验（多数处于I期和II期），但由于难以确定LSC的最佳靶点，相关结果仍受到限制。
It is now well known that the bone marrow (BM) cell niche contributes to leukemogenesis, but emerging data support the role of the complex crosstalk between AML cells and the BM microenvironment to induce a permissive immune setting that protects leukemic stem cells (LSCs) from therapy-induced death, thus favoring disease persistence and eventual relapse. The identification of potential immune targets on AML cells and the modulation of the BM environment could lead to enhanced anti-leukemic effects of drugs, immune system reactivation, and the restoration of AML surveillance. Potential targets and effectors of this immune-based therapy could be monoclonal antibodies directed against LSC antigens such as CD33, CD123, and CLL-1 (either as direct targets or via several bispecific T-cell engagers), immune checkpoint inhibitors acting on different co-inhibitory axes (alone or in combination with conventional AML drugs), and novel cellular therapies such as chimeric antigen receptor (CAR) T-cells designed against AML-specific antigens. Though dozens of clinical trials, mostly in phases I and II, are ongoing worldwide, results have still been negatively affected by difficulties in the identification of the optimal targets on LSCs.
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