Evaluation of the immunogenicity of ALDH(high) human head and neck squamous cell carcinoma cancer stem cells in vitro

Abstract

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.

Keywords: Aldehyde dehydrogenase (ALDH); Antibody; B cells; Cancer stem cells (CSC); Dendritic cells (DC); Head and neck squamous cell carcinoma (HNSCC); T cells.