CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题：The performance and perspectives of dendritic cell vaccines modified by immune checkpoint inhibitors or stimulants.
The performance and perspectives of dendritic cell vaccines modified by immune checkpoint inhibitors or stimulants.
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治疗性树突状细胞（DC）疫苗可刺激免疫系统清除肿瘤细胞。然而，尽管由DC疫苗诱导的抗原特异性T细胞反应通常可被观察到，但临床缓解率相对较差，因此需要对疫苗进行优化。有证据表明，免疫检查点对DC功能的抑制阻碍了DC疫苗介导的抗肿瘤免疫反应，最终导致肿瘤细胞的免疫逃逸。免疫检查点抑制剂（ICIs）和免疫检查点激活剂（ICAs）的使用扩展了免疫治疗的范围。已知大多数DC亚群均表达抑制性和刺激性检查点分子，因此可用于调控DC疫苗的有效性。此类调控已通过化疗、激动性或拮抗性抗体、siRNA、shRNA、CRISPR-Cas9、可溶性抗体、慢病毒和腺病毒等策略进行研究，以最大化DC疫苗的疗效。
因此，对免疫检查点的更深入理解可能有助于开发改进的DC疫苗。在此，我们综述了临床前研究中显示的各种ICIs或ICAs的作用，以及它们在DC疫苗中的潜在应用。
此外，还详细描述了用于阻断和刺激DCs中免疫检查点分子的新型治疗性干预策略。
Therapeutic dendritic cell (DC) vaccines stimulate the elimination of tumor cells by the immune system.
However, while antigen-specific T cell responses induced by DC vaccines are commonly observed, the clinical response rate is relatively poor, necessitating vaccine optimization. There is evidence that the suppression of DC function by immune checkpoints hinders the anti-tumor immune responses mediated by DC vaccines, ultimately leading to the immune escape of the tumor cells. The use of immune checkpoint inhibitors (ICIs) and immune checkpoint activators (ICAs) has extended the immunotherapeutic range.
It is known that both inhibitory and stimulatory checkpoint molecules are expressed by most DC subsets and can thus be used to manipulate the effectiveness of DC vaccines. Such manipulation has been investigated using strategies such as chemotherapy, agonistic or antagonistic antibodies, siRNA, shRNA, CRISPR-Cas9, soluble antibodies, lentiviruses, and adenoviruses to maximize the efficacy of DC vaccines.
Thus, a deeper understanding of immune checkpoints may assist in the development of improved DC vaccines.
Here, we review the actions of various ICIs or ICAs shown by preclinical studies, as well as their potential application in DC vaccines. New therapeutic interventional strategies for blocking and stimulating immune checkpoint molecules in DCs are also described in detail.
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