Evaluation of the immunogenicity of ALDHhigh human head and neck squamous cell carcinoma cancer stem cells in vitro. (August 2016)

• Record Type: Journal Article
• Authors: Prince, Mark E.P.; Zhou, Li; Moyer, Jeffrey S.; Tao, Huimin; Lu, Lin; Owen, John; Egenti, Martin; Zheng, Fang; Chang, Alfred E.; Xia, Jianchuan; Wolf, Gregory; Wicha, Max S.; Huang, Shiang; Ren, Xiubao; Li, Qiao
• Is Part Of: Oral oncology. Volume 59(2016:Aug.)
• Page Start: 30
• Page End: 42
• Publication Date: 2016-08
• Subjects: Head and neck squamous cell carcinoma (HNSCC) -- Cancer stem cells (CSC) -- Aldehyde dehydrogenase (ALDH) -- Dendritic cells (DC) -- T cells -- B cells -- Antibody; Mouth -- Cancer -- Periodicals; Mouth -- Tumors -- Periodicals; Mouth Diseases -- Periodicals; Mouth Neoplasms -- Periodicals; Bouche -- Cancer -- Périodiques; Bouche -- Tumeurs -- Périodiques; Tumeurs -- Périodiques; Electronic journals; 616.9943105
• DOI: 10.1016/j.oraloncology.2016.05.013
• Languages: English
• ISSNs: 1368-8375

Abstract

Highlights: CSC-DC vaccine-sensitized HNSCC patient PBMC T cells produce IFNγ against CSCs. CSC-DC vaccine-sensitized patient CTLs lyses autologous CSCs. CSC-DC vaccine-sensitized patient PBMC B cells produce antibody which binds to CSCs. We show that the immunogenicity of HNSCC CSC is distinct from that of non-CSCs. Our results suggest the existence of unique CSC antigens in the ALDH high HNSCC cells. Summary: Objectives: To establish the concept that the antigenicity/immunogenicity of ALDH high human head and neck squamous cell carcinoma (HNSCC) cancer stem cells (CSC) is distinct from that of ALDH low non-CSCs. Methods: We generated CSC-loaded dendritic cells (DCs) to sensitize autologous peripheral blood T, B lymphocytes to react with CSCs using human HNSCC samples in vitro . Results: From peripheral blood collected from patients with HNSCC, we obtained PBMCs. DCs generated from the PBMC and pulsed with the lysate of ALDH high cells isolated from cultured HNSCC cells (CSC-DC) could sensitize autologous T, B lymphocytes in vitro, which was evident by cytokine production, CTL activity, and antibody secretion of these primed T, B cells in response to ALDH high CSCs. In contrast, DCs pulsed with lysate of ALDH low cells (ALDH low -DC) resulted in limited sensitization/priming of autologous T, B lymphocytes to produce IFNγ, GM-CSF; lyse CSCs, and secrete IgM and IgG in response to ALDH high CSCs. These results demonstrated significant differences in the antigenicity/immunogenicity between ALDH high CSCs vs . ALDH low cells isolated from the tumor specimen of patients with HNSCC, which indicates the existence of unique CSC antigens in the ALDH high population. Conclusion: It is feasible to generate DCs from the PBMCs and isolate ALDH high CSCs from cultured tumor cells of the patients with HNSCC to prepare CSC-DC vaccines that can induce anti-HNSCC CSC cellular and humoral immunity, indicating its potential clinical application to treat patients with HNSCC.