Abstract 3124: Cytotoxic effects of tumor-specific T lymphocytes on autologous cancer initiator stem-like glioblastoma cells

Abstract

Abstract [Purpose] In clinical trial of autologous dendritic cell/autologous tumor cell antigens (ADCTA) adjuvant immunotherapy of glioblastoma multiforme (GBM), we studied if and how GBM CD133(+) stem-like initiator cells are susceptible to immune cytotoxic eradication [Methods] Tumor-infiltrating T lymphocytes (TILs) were isolated from GBM patients after the ADCTA vaccination and tested for their effects on CD133(+) and CD133(-) glioma cells separated from the same patients. [Results] TILs isolated from GBM patients after ADCTA vaccination were cytotoxic to both CD133(+) and CD133(-) autologous glioma cells. However, the cell lysis was detectable in CD133(-) in 4 hours but did not occur until more than 18 hours later in the CD133(+) cancer stem-like initiator cells. Surprisingly, we found that, upon exposure to the TILs, the GBM tumor cells showed phenotype shift from CD133(+) to CD133 (-). Similar CD133(+) to CD133(-) phenotype shift was also observed by exposure to culture condition medium of the TILs. The responsible factors secreted by the TILs that caused the phenotype shift was determined to be INFγ and TNFα. [Conclusion] ADCTA vaccination in GBM patients would generate TILs that are not only specifically cytotoxic to autologous CD133(-) glioma cells but also secret INFγ and TNFα etc to induce phenotypic shift of the resistant CD133(+) stem-like GBM to susceptible CD133(-) glioma cells. Citation Format: Yin-Cheng Huang, Kuo-Chen Wei, Chen-Nen Chang, Wen K. Yang. Cytotoxic effects of tumor-specific T lymphocytes on autologous cancer initiator stem-like glioblastoma cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3124.