Mark E P Prince1, Li Zhou1,2, Jeffrey S Moyer1, Huimin Tao1,3, Lin Lu1,4, John Owen1, Martin Etigen1, Fang Zheng1,3, Alfred E Chang1, Jianchuan Xia4, Gregory Wolf1, Max S Wicha1, Shiang Huang3, Xiubao Ren2, Qiao Li1. 1. University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan, USA. 2. Department of Immunology, Biotherapy Center ,Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Immunology and Biotherapy, Tianjin, P. R. China. 3. Hubei Province Stem Cell Research & Appling Center, Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. 4. State Key Laboratory of Oncology in Southern China and Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, China.
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.
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
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