Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; Division of Transplantation Immunology, National Research Institute for Child Health and Development, Tokyo, Japan.
Division of Transplantation Immunology, National Research Institute for Child Health and Development, Tokyo, Japan.
Neoplasia. 2023 May;39:100893. doi: 10.1016/j.neo.2023.100893. Epub 2023 Mar 7.
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.
树突状细胞（DCs）作为最有效的抗原提呈细胞，能够启动初始和记忆 T 细胞的激活。为了产生有效的抗肿瘤免疫，增强肿瘤相关树突状细胞（TADCs）的抗肿瘤活性或有效抑制 TADCs 使其保持免疫刺激性是至关重要的。联合磷脂（cPLs）佐剂可能通过激活 DCs 发挥作用。本研究阐明了 cPLs 佐剂抑制肿瘤生长的潜在机制，并证实 cPLs 佐剂能够诱导 BMDCs 的体外成熟和激活（上调 MHC-II、CD80、CD40、IL-1β、IL-12、IL-6 的表达）。然后，我们从实体瘤中分离肿瘤浸润淋巴细胞（TILs），并分析 TILs 的表型和细胞因子。对 TILs 的检查表明，cPLs 佐剂上调了 TADCs 上共刺激分子（MHC-II、CD86）和磷脂酰丝氨酸（PS）受体（TIM-4）的表达，增强了肿瘤驻留 T 细胞的细胞毒性效应（CD107a）和促炎细胞因子产生（IFN-γ、TNF-α、IL-2）。综上所述，cPLs 佐剂可能是癌症免疫治疗的一种免疫增强佐剂。该试剂可能会促使针对 DC 的癌症免疫治疗的新方法的发展。
