Boyuan Zou, Shaoyou Xia, Xiaohui Du, Yingxin Xu, Ning Ning, Songyan Li, Da Teng, Hao Li, Zilong Hu, Shidong Hu, Yufeng Wang
Department of Retroperitoneal Tumor Surgery, Peking University International Hospital, Beijing, China (mainland)
Med Sci Monit 2019; 25:5465-5472
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.
Keywords: Colorectal Neoplasms, Dendritic Cells, Immunotherapy, Adoptive, Tuftsin