Abstract 1410: Evaluation of the immunogenicity of ALDHhigh human head and neck squamous cell carcinoma cancer stem cells in vitro

Abstract

Abstract Using mouse models we reported that dendritic cells (DC) pulsed with cancer stem cells (CSC) enriched by virtue of their expression of the CSC marker aldehyde dehydrogenase (ALDH) significantly reduced development of pulmonary metastases and prolonged survival. In this recent study, we established the concept that the antigenicity/immunogenicity of ALDHhigh human head and neck squamous cell carcinoma (HNSCC) cancer stem cells is distinct from that of ALDHlow non-CSCs. To this end, we generated CSC-loaded DCs to sensitize autologous peripheral blood lymphocytes to react with CSCs using human HNSCC samples in vitro. From peripheral blood and paired tumor tissues collected from 9 patients with HNSCC, we obtained PBMCs and established 4 HNSCC tumor cell lines. DCs generated from the PBMC and pulsed with the lysate of ALDHhigh 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 ALDHhigh CSCs. In contrast, DCs pulsed with lysate of ALDHlow cells from the same HNSCC patient (ALDHlow-DC) resulted in limited sensitization/priming of autologous T, B lymphocytes to produce IFNγ, lyse CSCs, and secrete IgM and IgG in response to ALDHhigh CSCs. These results demonstrated significant differences in the antigenicity/immunogenicity between ALDHhigh CSCs vs. ALDHlow cells isolated from the tumor specimen of patients with HNSCC, which indicates the existence of unique CSC antigens in the ALDHhigh population. In addition, this study demonstrates that it is feasible to generate DCs from the PBMCs and isolate ALDHhigh CSCs from cultured tumor cells of the patients with HNSCC to prepare CSC-DC vaccines for clinical application. Citation Format: Mark E.P. Prince, Li Zhou, Yang Xia, Huimin Tao, Jeffrey S. Moyer, Lin Lu, John Owen, Alfred E. Chang, Jianchuan Xia, Gregory Wolf, Max S. Wicha, Xiubao Ren, Yangyi Bao, Shiang Huang, Qiao Li. Evaluation of the immunogenicity of ALDHhigh human head and neck squamous cell carcinoma cancer stem cells in vitro. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1410. doi:10.1158/1538-7445.AM2015-1410