Yang Jia, Eresen Aydin, Shangguan Junjie, Ma Quanhong, Zhang Zhuoli, Yaghmai Vahid
Department of Radiology, Feinberg School of Medicine, Northwestern University Chicago, IL 60611, USA.
Robert H. Lurie Comprehensive Cancer Center of Northwestern University Chicago, IL 60611, USA.
Am J Cancer Res. 2020 Nov 1;10(11):3911-3919. eCollection 2020.
It is unknown whether the route of administration impacts dendritic cell (DC)-based immunotherapy for pancreatic ductal adenocarcinoma (PDAC). We compared the effect of intraperitoneal (i.p.), subcutaneous (s.c.), and intratumoral (i.t.) administration of DC vaccine on induction of antitumor responses in a KPC mouse model of PDAC. Histological analysis and flow cytometry were used to evaluate tumor progression and antitumor immunity after different routes of DC vaccination. Using a flank mouse model of PDAC, we found that the i.t. route of DC vaccination had no significant effect on tumor growth rates compared with i.p. and s.c. routes (i.p. 6.66 ± 2.58% vs s.c. 6.79 ± 1.36% vs i.t. 8.57 ± 2.36%; P = 0.33). However, in an orthotopic PDAC model, i.p. injection of DC vaccine effectively suppressed tumor growth, inhibited tumor progression, and increased antitumor immunity compared with s.c. vaccination (tumor weight: i.p. 71.60 ± 15.55 mg vs control 200.40 ± 53.04 mg; P = 0.048; s.c. 151.40 ± 41.64 mg vs control 200.40 ± 53.04 mg; P = 0.49). Our study suggests that immunization via an i.p. route results in superior antitumor immune response and tumor suppression when compared with other routes.
给药途径是否会影响基于树突状细胞（DC）的胰腺导管腺癌（PDAC）免疫治疗尚不清楚。我们比较了腹腔内（i.p.）、皮下（s.c.）和瘤内（i.t.）注射DC疫苗对PDAC的KPC小鼠模型中抗肿瘤反应诱导的影响。采用组织学分析和流式细胞术评估不同DC疫苗接种途径后的肿瘤进展和抗肿瘤免疫。使用PDAC的侧腹小鼠模型，我们发现与i.p.和s.c.途径相比，i.t.途径的DC疫苗接种对肿瘤生长速率没有显著影响（i.p. 6.66±2.58% vs s.c. 6.79±1.36% vs i.t. 8.57±2.36%；P = 0.33）。然而，在原位PDAC模型中，与s.c.接种相比，i.p.注射DC疫苗可有效抑制肿瘤生长、抑制肿瘤进展并增强抗肿瘤免疫（肿瘤重量：i.p. 71.60±15.55 mg vs对照200.40±53.04 mg；P = 0.048；s.c. 151.40±41.64 mg vs对照200.40±53.04 mg；P = 0.49）。我们的研究表明，与其他途径相比，通过i.p.途径进行免疫可产生更好的抗肿瘤免疫反应和肿瘤抑制效果。
