免疫检查点阻断通过扩增效应 CD8⁺ T 细胞克隆增强淋巴细胞清除性化疗诱导的抗肿瘤免疫
Immune Checkpoint Blockade Augments Lymphodepleting Chemotherapy-Induced Antitumor Immunity by Expanding Effector CD8+ T-cell Clones.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Current "state of the art" on dendritic cell-based cancer vaccines in melanoma.
Current "state of the art" on dendritic cell-based cancer vaccines in melanoma.
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树突状细胞(DC)是免疫系统的守门人,在抗肿瘤免疫应答中不可或缺。近年来,借助单细胞测序方法,其分类已被大幅修订。在本综述中,我们聚焦于它们在癌症中的独特作用,以及如何操控特定的DC亚群以诱导有效且持久的抗肿瘤应答。
历史上,由于从外周血中易于分离获得足够数量的单核细胞来源DC,其在临床上作为治疗性癌症疫苗的效用曾被探索。然而,人们逐渐认识到,自然循环的髓系DC(myDC)在发挥其生理作用时,是功能更强大的抗原呈递细胞来源。随着免疫磁珠技术用于分离自然循环DC亚群的出现,这些myDC亚群的治疗价值目前正在被探索。由于肿瘤微环境中也需要DC来“重新授权”抗肿瘤T细胞的活性,因此DC疫苗的瘤内给药途径也在探索之中。此外,为避免使用昂贵的细胞疫苗,吸引DC进入肿瘤微环境的方法被认为有助于修复缺陷的癌症-免疫循环,因而受到关注。总结:近年来,用于疫苗接种的DC类型及其给药途径发生了显著演变。瘤内疫苗接种策略需要与额外的刺激联合使用,以确保DC在肿瘤微环境中正常发挥功能。此外,瘤内给药限制了其仅适用于具有可及病灶的患者。
PURPOSE OF REVIEW: Dendritic cells (DCs) are the gatekeepers of our immune system and indispensable in the antitumor immune response. In recent years, their classification has been revised considerably using single-cell sequencing approaches.
In this review, we focus on their unique role in cancer and how specific DC subsets can be manipulated to induce an effective and durable antitumor response. RECENT FINDINGS: Historically, due to the ease of their isolation in sufficient cell numbers from peripheral blood, the utility of monocyte-derived DCs as therapeutic cancer vaccines was explored in the clinic.
However, it became clear that naturally circulating myeloid DCs (myDC), exerting their physiological role, are a functionally more powerful cellular source of antigen presenting cells. With the advent of immunomagnetic bead technology to isolate naturally circulating DC subsets, the therapeutic value of these myDC subsets is currently being explored. Since DCs are also needed in the tumor microenvironment in order to "relicense" the activity of antitumor T cells, also intratumoral administration routes for DC vaccines are explored.
In addition, to circumvent the use of expensive cellular vaccines, approaches to attract DCs to the tumor microenvironment are considered of interest in order to repair a defective cancer-immunity cycle. SUMMARY: In recent years, the type of DCs used for vaccination and their administration route evolved considerably. Intratumoral vaccination strategies require combination with additional stimuli to ensure proper functioning of DCs in the tumor microenvironment.
Moreover, intratumoral administration limits the applicability to patients with accessible lesions.
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