CELL INTELLIGENCE · 肿瘤细胞治疗研究

Glioblastoma (GBM) is a grade IV glioma, which is the most malignant astrocytoma and originates from astrocytic glial cells. GBM tumors consist of a complex mixture of heterogeneous cells, complicating the search for the cell of origin. The acquisition and maintenance of the hallmarks of cancer depend, to various degrees, on the contributions from the tumor microenvironment (TME). This reliance on the TME offers an opportunity for therapeutic intervention by targeting TME elements or the signaling pathways. There is a significant therapeutic advantage in targeting the TME compared with directly targeting cancer cells, because cancer cells are prone to drug resistance due to their genomic instability. As an alternative approach, targeted therapies may limit unwanted toxicity, associated with conventional therapies and more effectively block the tumor proliferation. Although immunotherapy achieved some notable successes in the treatment of several malignancies such as melanoma and lung cancer, its efficacy in GBM remains limited due to BBB, low tumor mutational burden, an immunosuppressive TME, and profound intratumoral heterogeneity, contributing to therapeutic resistance. There are several modes of immunotherapy including restorative, adoptive cell transfer, passive, active, modulatory and immunogenic cell death (ICD) immunotherapies. The successful development of immunotherapeutics for GBM requires generating a robust antitumor immune response while overcoming T-cell anergy and tolerance. The immune system has various checkpoint pathways; thus, targeting multiple checkpoints simultaneously will have potential survival benefits.