<p>Immunotherapeutic methods, such as the use of checkpoint inhibitors, CAR T cells, dendritic cell vaccines, <i>etc</i>., offer promising approach to the treatment of glioblastomas. Dendritic cell (DC)-based vaccines used in glioma therapy have been well studied and are effective in some cases. However, the use of DC vaccines for the treatment of patients with gliomas, though shows promising results, is still limited by the suboptimal choice of tumor antigen and the method of its loading, as well as the immunosuppressive nature of the tumor cell microenvironment. In this work, we showed that glioma cell lines express a broad spectrum of immune checkpoints, suppress the maturation of allogeneic DCs during direct co-culturing, and do not stimulate the proliferation of allogeneic lymphocytes. Lymphocytes primed with dendritic cells loaded with the corresponding tumor lysates effectively lysed only two of three glioma cell lines, T98G and U373 MG, whereas 1321N1 cells completely suppressed the cytotoxic activity of lymphocytes primed by co-culturing with DCs loaded with the lysate of these cells. Thus, the efficacy of DC vaccines may be related to the individual characteristics of glioma cells.</p>

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Variability of the Immunosuppressive Properties of Glioma Cell Lines

  • I. V. Kholodenko,
  • R. Yu. Saryglar,
  • A. Y. Lupatov,
  • K. V. Kovalskaya,
  • O. A. Bystrykh,
  • A. V. Kuprin,
  • K. N. Yarygin

摘要

Immunotherapeutic methods, such as the use of checkpoint inhibitors, CAR T cells, dendritic cell vaccines, etc., offer promising approach to the treatment of glioblastomas. Dendritic cell (DC)-based vaccines used in glioma therapy have been well studied and are effective in some cases. However, the use of DC vaccines for the treatment of patients with gliomas, though shows promising results, is still limited by the suboptimal choice of tumor antigen and the method of its loading, as well as the immunosuppressive nature of the tumor cell microenvironment. In this work, we showed that glioma cell lines express a broad spectrum of immune checkpoints, suppress the maturation of allogeneic DCs during direct co-culturing, and do not stimulate the proliferation of allogeneic lymphocytes. Lymphocytes primed with dendritic cells loaded with the corresponding tumor lysates effectively lysed only two of three glioma cell lines, T98G and U373 MG, whereas 1321N1 cells completely suppressed the cytotoxic activity of lymphocytes primed by co-culturing with DCs loaded with the lysate of these cells. Thus, the efficacy of DC vaccines may be related to the individual characteristics of glioma cells.