肿瘤细胞治疗研究
英文原题：Modified Dendritic cells as a therapeutic platform in hematologic malignancies with translational insights from central nervous system tumors.
树突状细胞（DC）疫苗能引发特异性免疫反应，能够精确消除靶细胞。
树突状细胞（DC）疫苗能够激发特异性免疫应答，从而精准清除靶细胞。近年来，大量研究探索了DC疫苗接种用于治疗急性髓系白血病（AML）和骨髓增生异常综合征（MDS）等血液系统恶性肿瘤以及多种非白血病性癌症。DC主要通过两种策略加以利用——原位法和体外（经典）法——以增强抗肿瘤免疫。用于AML和MDS疫苗的主要DC亚型为单核细胞衍生DC和白血病衍生DC。多种肿瘤相关成分已被用作负载DC的抗原来源，包括肽段、重组蛋白、凋亡白血病细胞、全肿瘤细胞或裂解物，以及通过RNA电穿孔工程化改造以呈递更广泛抗原谱的DC/DCleu。为提高DC疫苗疗效，已开发出多种创新策略，包括与传统化疗、单特异性或双特异性抗体以及免疫检查点抑制剂的联合治疗。历经十余年的挑战，该领域已取得有意义的进展并展现出强大潜力。本综述总结了DC免疫治疗的最新进展，特别聚焦于血液系统恶性肿瘤，并纳入来自中枢神经系统肿瘤——尤其是胶质母细胞瘤——的比较性转化研究参考，以强调两者共同的免疫学障碍及独特的机制差异。树突状细胞（DC）是特化的免疫细胞，在机体防御癌症中发挥关键作用。研究人员已开发出使用修饰DC的疫苗，以训练免疫系统更有效地识别和清除癌细胞。这些疫苗已被研究用于治疗血液系统恶性肿瘤，如急性髓系白血病（AML）和骨髓增生异常综合征（MDS），以及脑肿瘤和其他实体癌。基于DC的癌症免疫治疗主要有两种应用方式：直接在体内刺激免疫系统（原位），或给予在实验室中制备的DC（ex vivo，即经典方法）。对于AML和MDS，最广泛使用的DC群体是来源于单核细胞的DC（moDC）或来源于白血病的树突状细胞（DCleu）。为提高疫苗效力，DC通常负载肿瘤相关抗原——如蛋白质或遗传物质——以增强免疫识别并促进更强的抗肿瘤反应。近年来的进展进一步提高了DC疫苗的治疗潜力，尤其是与化疗、单克隆抗体或其他免疫调节剂联合使用时。经过数十年的研究，在将基于DC的疫苗确立为可行的癌症治疗策略方面已取得有意义的进展。本综述总结了这一前景广阔领域的最新进展，强调其未来有助于实现更有效癌症治疗的潜力。
Dendritic cell (DC) vaccines elicit specific immune responses capable of precisely eliminating target cells. In recent years, numerous studies have explored the use of DC vaccination for treating hematological malignancies such as acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), as well as various non-leukemic cancers. DCs are utilized primarily through two strategies-in situ and ex vivo (canonical) approaches-to enhance anticancer immunity. The main DC subtypes employed in vaccines for AML and MDS are monocyte-derived DCs and leukemia-derived DCs. Various tumor-associated components have been used as antigen sources to load DCs, including peptides, recombinant proteins, apoptotic leukemic cells, whole tumor cells or lysates, and DCs/DCleu engineered to present a broader antigenic repertoire via RNA electroporation. Innovative strategies have been developed to improve DC vaccine efficacy, including combination therapies with conventional chemotherapy, monospecific or bispecific antibodies, and immune checkpoint inhibitors. Following a decade of challenges, the field has achieved meaningful progress and shows strong potential. This review summarizes recent advances in DC-based immunotherapy with a specific focus on hematologic malignancies, and incorporating comparative translational references from central nervous system tumors most notably glioblastoma to underscore both the common immunologic barriers and the unique mechanistic distinctions. Dendritic cells (DCs) are specialized immune cells that play a critical role in the body’s defense against cancer. Researchers have developed vaccines using modified DCs to train the immune system to recognize and eliminate cancer cells more effectively. These vaccines have been investigated for the treatment of hematologic malignancies such as acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), as well as for brain tumors and other solid cancers.DC-based cancer immunotherapy can be applied in two main ways: by stimulating the immune system directly within the body (in situ) or by administering DCs prepared in the laboratory ( ex vivo , the canonical approach). For AML and MDS, the most widely used DC populations are those derived from monocytes (moDCs) or from leukemia-derived dendritic cells (DCleu). To improve vaccine efficacy, DCs are typically loaded with tumor-associated antigens—such as proteins or genetic material—that enhance immune recognition and promote a more robust antitumor response.Recent advances have further increased the therapeutic potential of DC vaccines, particularly when combined with chemotherapy, monoclonal antibodies, or other immune-modulating agents. After decades of investigation, meaningful progress has been achieved in establishing DC-based vaccines as a viable strategy for cancer treatment. This review summarizes the most recent developments in this promising field, highlighting their potential to contribute to more effective cancer therapies in the future.
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