Department of Hematology, Zealand University Hospital, Sygehusvej 10, 4000, Roskilde, Denmark.
Center for Cancer Immune Therapy, Department of Hematology, Herlev Hospital, Herlev, Denmark.
Semin Immunopathol. 2019 Jan;41(1):97-109. doi: 10.1007/s00281-018-0693-x. Epub 2018 Jul 9.
The myelodysplastic syndromes, the chronic myeloproliferative neoplasms, and the acute myeloid leukemia are malignancies of the myeloid hematopoietic stem cells of the bone marrow. The diseases are characterized by a dysregulation of the immune system as both the cytokine milieu, immune phenotype, immune regulation, and expression of genes related to immune cell functions are deregulated. Several treatment strategies try to circumvent this deregulation, and several clinical and preclinical trials have shown promising results, albeit not in the same scale as chimeric antigen receptor T cells have had in the treatment of refractory lymphoid malignancies. The use of immune checkpoint blocking antibodies especially in combination with hypomethylating agents has had some success-a success that will likely be enhanced by therapeutic cancer vaccination with tumor-specific antigens. In the chronic myeloproliferative neoplasms, the recent identification of immune responses against the Januskinase-2 and calreticulin exon 9 driver mutations could also be used in the vaccination setting to enhance the anti-tumor immune response. This immune response could probably be enhanced by the concurrent use of immune checkpoint inhibitors or by vaccination with epitopes from immune regulatory proteins such as arginase-1 and programmed death ligand-1. Herein, we provide an overview of current cancer immune therapeutic treatment strategies as well as potential future cancer immune therapeutic treatment options for the myeloid malignancies.
骨髓增生异常综合征、慢性髓系增殖性肿瘤和急性髓系白血病是骨髓髓系造血干细胞的恶性肿瘤。这些疾病的特征是免疫系统失调，细胞因子微环境、免疫表型、免疫调节以及与免疫细胞功能相关的基因表达均失调。几种治疗策略试图规避这种失调，一些临床前和临床试验已经显示出有希望的结果，尽管其规模不如嵌合抗原受体 T 细胞在治疗难治性淋巴恶性肿瘤方面的规模。免疫检查点阻断抗体的使用，特别是与低甲基化剂联合使用，已经取得了一些成功——这一成功可能会因针对肿瘤特异性抗原的治疗性癌症疫苗而得到增强。在慢性髓系增殖性肿瘤中，最近对 Janus 激酶-2 和钙网蛋白外显子 9 驱动突变的免疫反应的识别也可以在疫苗接种环境中使用，以增强抗肿瘤免疫反应。这种免疫反应可能通过同时使用免疫检查点抑制剂或用免疫调节蛋白（如精氨酸酶-1 和程序性死亡配体-1）的表位进行疫苗接种来增强。在此，我们概述了当前的癌症免疫治疗策略，以及髓系恶性肿瘤的潜在未来癌症免疫治疗选择。
