Glioma associated microglia/macrophages (GAMs) constitute the largest proportion of glioma infiltrating cells, par-ticularly in high grade tumors (i.e., glioblastoma). Once inside the tumors, GAMs usually acquire a sp...Glioma associated microglia/macrophages (GAMs) constitute the largest proportion of glioma infiltrating cells, par-ticularly in high grade tumors (i.e., glioblastoma). Once inside the tumors, GAMs usually acquire a specific pheno-type of activation that favors tumor growth, angiogenesis and promotes the invasion of normal brain parenchyma. Therefore, treatments that limit or prevent GAMs' recruitment at the tumor site or modulate their immune activa-tion promoting antitumor activities are expected to exert beneficial effects in glioblastoma. In the present paper, we aim at the revision of pharmacological strategies that interfere with GAMs' function and are currently proposed as an alternative/additional option to current approved cytotoxic regimens.展开更多
Microglia and macrophages, two myeloid cell lineages with different origins, make up the majority of immune cells present in glioblastoma (GBM). However, much of the literature does not distinguish between microglia a...Microglia and macrophages, two myeloid cell lineages with different origins, make up the majority of immune cells present in glioblastoma (GBM). However, much of the literature does not distinguish between microglia and macrophages, despite a growing body of evidence that demonstrates key structural and functional differences between the cell types. Furthermore, the current M1/M2 paradigm used to sub-classify microglia and macrophages has proven to be incomplete at best, with the growing amount of in vivo and genomic data incompatible with this dichotomy. Finally, a number of studies have already established that in the setting of the GBM tumor microenvironment, both microglia and macrophages are complicit in tumor progression. This review highlights the differences between microglia and macrophages, particularly in the context of GBM, and discusses at length several potential therapeutic strategies made possible by understanding specific pro-tumor and anti-tumor pathways in these myeloid populations. Ultimately, investigating the differences between microglia and macrophages offers insight into the progression of GBM, its marked resistance to current immunotherapy regimens, and future directions for new treatment modalities.展开更多
文摘Glioma associated microglia/macrophages (GAMs) constitute the largest proportion of glioma infiltrating cells, par-ticularly in high grade tumors (i.e., glioblastoma). Once inside the tumors, GAMs usually acquire a specific pheno-type of activation that favors tumor growth, angiogenesis and promotes the invasion of normal brain parenchyma. Therefore, treatments that limit or prevent GAMs' recruitment at the tumor site or modulate their immune activa-tion promoting antitumor activities are expected to exert beneficial effects in glioblastoma. In the present paper, we aim at the revision of pharmacological strategies that interfere with GAMs' function and are currently proposed as an alternative/additional option to current approved cytotoxic regimens.
文摘Microglia and macrophages, two myeloid cell lineages with different origins, make up the majority of immune cells present in glioblastoma (GBM). However, much of the literature does not distinguish between microglia and macrophages, despite a growing body of evidence that demonstrates key structural and functional differences between the cell types. Furthermore, the current M1/M2 paradigm used to sub-classify microglia and macrophages has proven to be incomplete at best, with the growing amount of in vivo and genomic data incompatible with this dichotomy. Finally, a number of studies have already established that in the setting of the GBM tumor microenvironment, both microglia and macrophages are complicit in tumor progression. This review highlights the differences between microglia and macrophages, particularly in the context of GBM, and discusses at length several potential therapeutic strategies made possible by understanding specific pro-tumor and anti-tumor pathways in these myeloid populations. Ultimately, investigating the differences between microglia and macrophages offers insight into the progression of GBM, its marked resistance to current immunotherapy regimens, and future directions for new treatment modalities.
