Preparation of a Plasma-Induced Dendritic Cell Vaccine and its Anti-Tumor Immunity in a Murine Model of Melanoma

IF 3.7 4区医学 Q2 PHARMACOLOGY & PHARMACY

Advanced Therapeutics Pub Date : 2024-09-09 DOI:10.1002/adtp.202400142

Xiangni Wang, Jinren Liu, Xiying Wang, Jiajia Lu, Guimin Xu, Yixin Cui, Zhirou He, Yulin Xu, Xingmin Shi, Guanjun Zhang

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Abstract

Dendritic cell (DC) vaccines play an important role in anti-tumor immunotherapy. Tumor-associated cells or cytokines in the tumor microenvironment (TME) can inhibit the antigen-presenting function of DC. Immunogenic cell death (ICD) can enhance the uptake and presentation of tumor antigens by DC. This study investigates the maturation mechanism of DC induced by low-temperature plasma (LTP), as well as the therapeutic and protective effects of LTP-induced DC vaccine in a tumor model. DC2.4 that is co-cultured with LTP-treated B16F10 (LTP-B16) or with these supernatants exhibited decreased phagocytic activity, increased production of cytokines (IL-12, IL-6, TNF-α, and IL-1β), and increased expression of cell surface activation markers (CD80, CD86, and MHC II). The expression of CD80⁺/CD86⁺ is decreased after pre-treatment with TLR4 and NF-κB (p65) inhibitors, respectively. In vivo, trials indicated that the LTP-induced DC vaccine-induced anti-tumor immunity and, when combined with cisplatin, synergistically reduced tumor growth.

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血浆诱导树突状细胞疫苗的制备及其在小鼠黑色素瘤模型中的抗肿瘤免疫作用

树突状细胞（DC）疫苗在抗肿瘤免疫疗法中发挥着重要作用。肿瘤微环境（TME）中的肿瘤相关细胞或细胞因子会抑制树突状细胞的抗原呈递功能。免疫原性细胞死亡（ICD）可增强DC对肿瘤抗原的摄取和呈递。本研究探讨了低温等离子体（LTP）诱导的DC成熟机制，以及LTP诱导的DC疫苗在肿瘤模型中的治疗和保护作用。与经 LTP 处理的 B16F10（LTP-B16）或这些上清液共培养的 DC2.4 表现出吞噬活性降低、细胞因子（IL-12、IL-6、TNF-α 和 IL-1β）产生增加以及细胞表面活化标记物（CD80、CD86 和 MHC II）表达增加。在使用 TLR4 和 NF-κB (p65) 抑制剂进行预处理后，CD80+/CD86+ 的表达量会分别减少。体内试验表明，LTP 诱导的 DC 疫苗可诱导抗肿瘤免疫，与顺铂联合使用时，可协同减少肿瘤生长。

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来源期刊

Advanced Therapeutics Pharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science

CiteScore

7.10

自引率

2.20%

发文量

130