Combined phospholipids adjuvant augments anti-tumor immune responses through activated tumor-associated dendritic cells.
Combined phospholipids adjuvant augments anti-tumor immune responses through activated tumor-associated dendritic cells.
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DOI：
10.1016/j.neo.2023.100893
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发表时间：
2023-05
期刊：
影响因子：
4.8
通讯作者：
Li, Xiao-Kang
中科院分区：
文献类型：
--
作者：
Shui, Yifang;Hu, Xin;Hirano, Hiroshi;Tsukamoto, Hirotake;Guo, Wen-Zhi;Hasumif, Kenichiro;Ijima, Fumihiro;Fujino, Masayuki;Li, Xiao-Kang
关键词：
cPL增强抗肿瘤免疫应答。cPL将TADC的表型从抑制性改变为促进性。cPL增强TIL中细胞因子的产生。cPL在体内改善DC对T细胞的抗原特异性引发。树突状细胞（Dendritic cells，DCs）作为最强的抗原提呈细胞，可以启动幼稚T细胞和记忆T细胞的活化。为了有效的抗肿瘤免疫，增强肿瘤相关DC（TADCs）的抗肿瘤活性或有效地抑制TADCs以使其保持免疫刺激细胞是必需的。组合磷脂（cPL）佐剂可通过活化DC起作用。本研究揭示了cPLs佐剂抑制肿瘤生长的潜在机制，证实cPLs佐剂可诱导体外培养的BMDCs成熟和活化（上调MHC-II、CD 80、CD 40、IL-1β、IL-12、IL-6的表达）。然后从实体瘤中分离肿瘤浸润淋巴细胞（TIL），并对其表型和细胞因子进行分析。对TIL的检查显示，cPL佐剂上调了TADC上的共刺激分子（MHC-II、CD 86）、磷脂酰丝氨酸（PS）受体（TIM-4）的表达，并增强了肿瘤驻留T细胞的细胞毒性效应（CD 107 a）以及促炎细胞因子（IFN-γ、TNF-α、IL-2）的产生。综上所述，cPL佐剂可能是用于癌症免疫治疗的免疫增强佐剂。该试剂可能会导致DC靶向癌症免疫治疗新方法的开发。
cPLs augments the anti-tumor immune responses. cPLs changes the phenotype of TADCs from suppressive to promotive. cPLs enhances the production of cytokine in the TILs. cPLs improves DCs’ antigen-speacific priming of T cells in vivo. Dendritic cells (DCs) can initiate both naïve and memory T cell activation, as the most potent antigen-presenting cells. For efficient anti-tumor immunity, it is essential to enhance the anti-tumoral activity of tumor-associated DCs (TADCs) or to potently restrain TADCs so that they remain immuno-stimulating cells. Combined phospholipids (cPLs) adjuvant may act through the activation of DCs. This study demonstrated the potential mechanism of tumor growth inhibition of cPLs adjuvant, and confirmed that cPLs adjuvant could induce the maturation and activation (upregulation of MHC-II, CD80, CD40, IL-1β, IL-12, IL-6 expression) of BMDCs in vitro. Then we isolated tumor infiltrating lymphocytes (TILs) from solid tumor and analyzed the phenotype and cytokines of TILs. The examination of the TILs revealed that cPLs adjuvant upregulated the expression of co-stimulatory molecules (MHC-II, CD86), phosphatidylserine (PS) receptor (TIM-4) on TADCs and enhanced the cytotoxic effect (CD107a), as well as pro-inflammatory cytokine production (IFN-γ, TNF-α, IL-2) by the tumor-resident T cells. Taken together, cPLs adjuvant may be an immune-potentiating adjuvant for cancer immunotherapy. This reagent may lead to the development of new approaches in DC-targeted cancer immunotherapy.
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DOI：
10.1016/j.bbrc.2009.06.010
发表时间：
2009-08-14
影响因子：
3.1
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影响因子：
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DOI：
10.1084/jem.20200264
发表时间：
2021-01-04
期刊：
The Journal of experimental medicine
影响因子：
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DOI：
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发表时间：
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期刊：
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