The immunosuppressive microenvironment as the most important barrier against CAR T cell therapy of glioblastoma; a systematic review

Introduction Chimeric Antigen Receptor (CAR) T cell therapy has recently been introduced as a promising immunotherapy method against malignancies including Glioblastoma (GBM), the most aggressive form of brain tumors; however, it has shown limited efficacy against GBM. Objectives In this study, we will investigate obstacles that attenuate the efficacy of CAR T cells against GBM to improve its efficacy. Methods PubMed, Elsevier, and Google Scholar were searched in English with 4 keywords: chimeric antigen receptor, Glioblastoma, obstacles, and microenvironment from 2010 to May 2018. 30 articles were found regarding our inclusion criteria and 12 articles were included regarding our exclusion criteria. Result CAR T cell therapy has shown limited efficacy against GBM. Studies have demonstrated some obstacles to challenge the maximal efficacy of CAR therapy against GBM. Among multiple obstacles, the GBM immunosuppressive microenvironment is the most important factor that inhibits the maximal efficacy of CAR T cells. The immunosuppressive microenvironment of the GBM includes several immunosuppressive soluble factors such as transforming growth factor-β (TGF-β), IL-10, and IL-6. Immunosuppressive cells such as regulatory T cell (T-regs), myeloid-derived suppressor cells (MDSCs), and tumor-associated macrophages (TAMs) have reported suppressing the immune system. Also, the hypoxia-induced stress is an important metabolic barrier that causes the exhaustion of CAR T cells. ConclusionGlioblastoma immunosuppressive microenvironment involves various barriers that limit the function of CAR T cells. Thus, it seems that application of new generations of CAR T cells to overcome the immunosuppressive microenvironment of GBM could improve the efficacy of this method.

کلیدواژه ها:

Chimeric antigen receptor ، Glioblastoma ، Immunotherapy ، Microenvironment