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Generation of CAR T Cells for Adoptive Therapy in the Context of Glioblastoma Standard of Care
Published on: February 16, 2015
T-lymphocytes from focused ultrasound ablation subsequently mediate cellular antitumor immunity after adoptive cell
Li-Feng Ran1,2, Xun-Peng Xie2,3, Ji-Zhu Xia2
1Clinical HIFU Center for Tumor Therapy, Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
Background:
Our previous studies found that high-intensity focused ultrasound (HIFU) stimulated tumor-specific T cells in a mouse H22 tumor model, and adoptive transfer of the T cells from HIFU-treated mice could subsequently elicit stronger inhibition on the growth and progression of the implanted tumors. The aim of this study was to investigate the mechanism of T cells from focused ultrasound ablation in HIFU-mediated immunomodulation.
Methods:
Sixty H22 tumor-bearing mice were treated by either HIFU or sham-HIFU, and 30 naïve syngeneic mice served as controls. All mice were euthanized on day 14 after HIFU and splenic T cell suspensions were obtained in each group. Using an adoptive cell transfer model, a total of 1 × 106 T cells from HIFU treated-mice were intravenously injected into each syngeneic H22 tumor-bearing mouse twice on day 3 and 4, followed by the sacrifice for immunological assessments at 14 days after the adoptive transfer.
Results:
T cells from HIFU-treated mice could significantly enhance the cytotoxicity of CTLs (p < 0.001), with a significant increase of TNF-α (p < 0.001) and IFN-γ secretion (p < 0.001). Compared to control and sham-HIFU groups, the number of Fas ligand+ and perforin+ tumor-infiltrating lymphocytes (TILs) and apoptotic H22 tumor cells were significantly higher (p < 0.001) in the HIFU group. There were linear correlations between apoptotic tumor cells and Fas ligand+ TILs (r = 0.9145, p < 0.001) and perforin+ TILs (r = 0.9619, p < 0.001).
Conclusion:
T cells from HIFU-treated mice can subsequently mediate cellular antitumor immunity, which may play an important role in the HIFU-based immunomodulation.
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