Hu Zilong, Ma Yue, Shang Zhiyang, Hu Shidong, Liang Kai, Liang Wentao, Xing Xiaowei, Wang Yufeng, Du Xiaohui
Department of General Surgery, Chinese People's Liberation Army General Hospital, Beijing 100853, P.R. China.
Department of Tumor Prevention and Rehabilitation, PKU Care Rehabilitation Hospital, Beijing 102206, P.R. China.
Oncol Lett. 2018 Apr;15(4):5345-5351. doi: 10.3892/ol.2018.7978. Epub 2018 Feb 7.
Monoclonal antibodies recognizing programmed death-ligand 1 (PD-L1) have been used for the clinical treatment of diverse tumor types as a form of immune checkpoint inhibitor, with a favorable therapeutic effect. Dendritic cells (DCs) are potent antigen-presenting cells that serve a pivotal role in the activation of T cells, particularly cytotoxic T lymphocytes (CTLs). DC vaccines loaded with tumor antigens, DC-CTLs and activated T cells have been revealed to be a safe and effective treatment approach against colorectal cancer within a clinical setting. In addition to tumor cells, PD-L1 is also highly expressed on DCs. As research examining the association between anti-PD-L1 and DCs is lacking, the present study compared the expression of PD-L1 on DCs in the peripheral blood of healthy donors and patients with colorectal cancer. Following the application of anti-PD-L1, the DC phenotypes, function of DC-mediated T cell induction and the cytotoxicity of CTLs were investigated by flow cytometry. The present study revealed that treatment with anti-PD-L1 may promote the maturation of DCs and enhance the functionality of the DC1 subtype. It may also increase the number of CTLs that are activated and produce CTL cells with more potent anti-tumor activity. Therefore, the creation of DC vaccines in conjunction with anti-PD-L1 may be an effective future treatment strategy for patients with colorectal cancer.
识别程序性死亡配体1(PD-L1)的单克隆抗体已作为一种免疫检查点抑制剂用于多种肿瘤类型的临床治疗,具有良好的治疗效果。树突状细胞(DC)是强大的抗原呈递细胞,在T细胞尤其是细胞毒性T淋巴细胞(CTL)的激活中起关键作用。负载肿瘤抗原的DC疫苗、DC-CTL和活化的T细胞已被证明是临床环境中治疗结直肠癌的一种安全有效的方法。除肿瘤细胞外,PD-L1在DC上也高度表达。由于缺乏关于抗PD-L1与DC之间关联的研究,本研究比较了健康供体和结直肠癌患者外周血DC上PD-L1的表达。应用抗PD-L1后,通过流式细胞术研究DC表型、DC介导的T细胞诱导功能以及CTL的细胞毒性。本研究表明,抗PD-L1治疗可能促进DC成熟并增强DC1亚型的功能。它还可能增加被激活的CTL数量,并产生具有更强抗肿瘤活性的CTL细胞。因此,联合抗PD-L1制备DC疫苗可能是未来治疗结直肠癌患者的有效策略。