Department of Retroperitoneal Tumor Surgery, Peking University International Hospital, Beijing, China (mainland).
Department of General Surgery, The General Hospital of People's Liberation Army, Beijing, China (mainland).
Med Sci Monit. 2019 Jul 23;25:5465-5472. doi: 10.12659/MSM.915037.
BACKGROUND The aim of this study was to investigate the effect of antigenic peptides on dendritic cell maturation and activation as well as the role of dendritic cell induced cell function. The tumor-specific cytotoxic T lymphocytes induced by activation of the dendritic cells were also evaluated. MATERIAL AND METHODS SW-480 cell lysate and peptide antigens were selected as adjuvants in dendritic cell sensitization, and tuftsin was used to induce the phagocytosis of dendritic cells. Immature dendritic cells were stimulated with the antigen and adjuvant as follows: group A was negative control; group B was SW-480 (20 μg/mL); group C was SW-480 (20 μg/mL)+tumor necrosis factor (TNF)-alpha (10 μg/mL); group D was SW-480 (20 μg/mL)+tuftsin (20 μg/mL); group E was antigen peptide (2 μg/mL); group F was antigen peptide (2 μg/mL)+TNF-alpha (10 μg/mL); group G was antigen peptide (2 μg/mL)+tuftsin (20 μg/mL). Cytotoxic T lymphocytes activation and in vitro anti-tumor effects were examined by detecting the maturation marks of dendritic cells as well as interleukin (IL)-10 and IL-12 levels secreted by dendritic cells. Cells with the strongest immunizing effects were injected into nude mice and tumor suppression status was evaluated. RESULTS Group D (SW-480+tuftsin), group E (antigen peptides), group F (antigen peptide+TNF-alpha), and group G (antigen peptides+tuftsin) displayed significant differences compared to the control group (P<0.05). Group G (antigen peptides+tuftsin) could also promote the secretion of cytokines IL-12, as well as inhibit cytokine IL-10 secretion, compared to the other experimental groups (P<0.05). In the in vivo experiments of tumor inhibitions, antigenic polypeptide+tuftsin was the most effective (P<0.05). CONCLUSIONS Combination of cytotoxic T lymphocytes and T peptide therapy in treating human colorectal cancer might be used as a new treatment strategy based on adoptive cellular immunotherapy.
本研究旨在探讨抗原肽对树突状细胞成熟和激活的影响,以及树突状细胞诱导的细胞功能的作用。还评估了由树突状细胞激活诱导的肿瘤特异性细胞毒性 T 淋巴细胞。
SW-480 细胞裂解物和肽抗原被选为树突状细胞致敏的佐剂,而 tuftsin 用于诱导树突状细胞的吞噬作用。用抗原和佐剂刺激未成熟的树突状细胞:A 组为阴性对照;B 组为 SW-480(20 μg/mL);C 组为 SW-480(20 μg/mL)+肿瘤坏死因子(TNF)-α(10 μg/mL);D 组为 SW-480(20 μg/mL)+tuftsin(20 μg/mL);E 组为抗原肽(2 μg/mL);F 组为抗原肽(2 μg/mL)+TNF-α(10 μg/mL);G 组为抗原肽(2 μg/mL)+tuftsin(20 μg/mL)。通过检测树突状细胞成熟标志以及树突状细胞分泌的白细胞介素(IL)-10 和 IL-12 水平来检测细胞毒性 T 淋巴细胞的激活和体外抗肿瘤作用。将免疫效果最强的细胞注入裸鼠体内,并评估肿瘤抑制状态。
与对照组相比,D 组(SW-480+tuftsin)、E 组(抗原肽)、F 组(抗原肽+TNF-α)和 G 组(抗原肽+tuftsin)差异有统计学意义(P<0.05)。与其他实验组相比,G 组(抗原肽+tuftsin)还能促进细胞因子 IL-12 的分泌,并抑制细胞因子 IL-10 的分泌(P<0.05)。在肿瘤抑制的体内实验中,抗原多肽+tuftsin 是最有效的(P<0.05)。
细胞毒性 T 淋巴细胞与 T 肽联合治疗人结直肠癌可能成为基于过继细胞免疫治疗的新治疗策略。