肿瘤细胞治疗研究
英文原题：Harnessing dendritic cells (DCs) for melanoma immunotherapy: From basic biology to clinical strategies.
黑色素瘤作为一种免疫原性皮肤癌，是癌症免疫治疗中备受关注的领域。
黑色素瘤作为一种免疫原性皮肤癌，是癌症免疫治疗中备受关注的领域。免疫检查点抑制剂（ICIs）已在部分患者中改善了临床结局，但耐药或疾病复发仍是一个问题。树突状细胞（DCs）具有增强抗肿瘤免疫的潜力，因为它们是最有效的抗原呈递细胞，能够致敏并激活肿瘤特异性T细胞。近期单细胞技术的进展使我们能够全面表征肿瘤浸润DC亚群（经典1型（cDC1s）和cDC2s、浆细胞样（pDCs）、单核细胞来源（moDCs），以及潜在的新亚群如DC3s），并表征它们在促进黑色素瘤发展、逃避免疫监视和/或对治疗应答能力方面的不同作用。DCs能够捕获、加工并呈递抗原，以激活和调控T细胞介导的免疫应答，而控制黑色素瘤需要T细胞免疫。因此，下一代基于DC的免疫治疗方法正在被研究。这些方法包括利用自然循环DC亚群（即CD1c⁺ mDCs、活化pDCs）的疫苗，以及负载肿瘤特异性新抗原或mRNA的DCs，还包括含有toll样受体（TLR）配体、STING通路激动剂、纳米颗粒和溶瘤病毒的方法，以增强DC成熟和抗原呈递。此外，DC将与ICIs、过继性T细胞治疗或化疗等治疗联合，以诱导增强的协同免疫反应。在这篇综述中，我们总结了DC亚群在黑色素瘤中的功能、肿瘤微环境中DC功能障碍的潜在机制，以及下一代基于DC疗法的最新进展。我们还强调需要临床转化，并确定黑色素瘤疫苗个体化以及甚至与现有疗法联合治疗中的障碍和挑战，这些治疗需考虑DC生物学的潜力。
Melanoma, as an immunogenic skin cancer, is an area of great interest in cancer immunotherapy. Immune checkpoint inhibitors (ICIs) have resulted in improved clinical outcomes in selected patients, but resistance or relapsing disease remains a problem. Dendritic cells (DCs) have the potential to enhance antitumor immunity since they are the most potent antigen-presenting cells and can prime and activate tumor-specific T cells. Recent advancements in single-cell technologies have enabled us to characterize tumor-infiltrating DC subsets (conventional type 1 (cDC1s) and cDC2s, plasmacytoid (pDCs), monocyte-derived (moDCs), as well as potentially novel subsets like DC3s) entirely and characterize their distinct roles in promoting melanoma development, evading immune surveillance, and/or their ability to respond to therapy. DCs can capture, process, and present antigens to activate and regulate T-cell-mediated immune responses, with T-cell immunity needed to control melanoma. Consequently, Next-generation DC-based immunotherapy approaches are being examined. These approaches involve vaccines that utilize naturally circulating DC subsets (ie, CD1c⁺ mDCs, activated pDCs) as well as DCs charged with tumor-specific neoantigens or mRNA, and approaches containing toll-like receptor (TLR) ligands, STING pathway agonists, nanoparticles, and oncolytic viruses to enhance DC maturation and antigen presentation. Furthermore, DC will be combined with treatments including ICIs, adoptive T cell therapy, or chemotherapy to induce enhanced synergistic immune reactions. In this review, we summarize the DC subset functions in melanoma, the underlying mechanisms of DC dysfunction in the tumor microenvironment, and the most recent updates on next-generation DC-based therapies. We also highlight the need for clinical translation and determining barriers and challenges in the personalization of melanoma vaccines and even combination treatment with pre-existing therapies that consider the potential of DC biology.
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