Abstract
Recent efforts in brain tumor research have been directed towards the modulation of the immune system for therapeutic interventions. Several human cancers, including gliomas, are infiltrated with immune cell types—including neutrophils and myeloid-derived suppressor cells—that contribute to tumor progression, invasiveness, and treatment resistance. The role of tumor-associated neutrophils and myeloid-derived suppressor cells in cancer biology remains elusive, as these cells can exert a multitude of pro-tumor and antitumor effects. In this review, we provide the current understanding and novel insights on the role of neutrophils and myeloid-derived suppressor cells in glioma progression and treatment resistance, as well as the mechanisms of pleiotropic behaviors in these cells during disease progression, with an emphasis on possible strategies to reprogram these cells towards their antitumor actions.
Highlights
Gliomas represent approximately 80% of malignant brain tumors, which are classified into four major clinical grades, on the basis of their histologic characteristics and clinical behavior [1]
It has become increasingly clear that TANs play a major role in cancer biology and treatment
Despite the large amount of literature suggesting that neutrophils have pro-tumor effects, evidence from multiple studies has shown that these cells can be reprogrammed to kill tumor cells [28,30,33,52,63,130]
Summary
Gliomas represent approximately 80% of malignant brain tumors, which are classified into four major clinical grades (grades I–IV), on the basis of their histologic characteristics and clinical behavior [1]. In the revised World Health Organization classification of central nervous system tumors, a multidimensional approach was taken for the categorization of gliomas, integrating both histologic and genetic information to define tumor grades and their prognosis [2]. Grade IV glioma or glioblastoma (GBM) is the most common lethal primary brain tumor in adults, with a median survival time ranging from 12 to 15 months, with current standard of care treatment, which includes maximum surgical resection followed by concomitant chemotherapy and radiation therapy (RT). Single-cell RNA sequencing revealed that multiple subtypes could exist within a tumor, which substantially contributes to the inter- and intra-tumor heterogeneity of GBM/glioma [7]. NE: neutrophil elastase, TNFα: tumor necrosis factor alpha, H2O2: hydrogen peroxide, MMP9: matrix metallopeptidase 9, NO: nitric oxide, and NOS2: nitric oxide synthase 2
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