Evaluation of the immunogenicity of aldhhigh human head and neck squamous cell carcinoma cancer stem cells in vitro

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.