Improving immunotherapy for colorectal cancer using dendritic cells combined with anti-programmed death-ligand in vitro

Oncol Lett. 2018 Apr;15(4):5345-5351. doi: 10.3892/ol.2018.7978. Epub 2018 Feb 7.

Abstract

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.

Keywords: anti-programmed death-ligand 1; colorectal cancer; dendritic cells; immunotherapy.