TY - JOUR

T1 - Tumor-associated microglia and macrophages in the glioblastoma microenvironment and their implications for therapy

AU - Andersen, Rikke Sick

AU - Anand, Atul

AU - Harwood, Dylan Scott Lykke

AU - Kristensen, Bjarne Winther

N1 - Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2021

Y1 - 2021

N2 - Glioblastoma is the most frequent and malignant primary brain tumor. Standard of care includes surgery followed by radiation and temozolomide chemotherapy. Despite treatment, patients have a poor prognosis with a median survival of less than 15 months. The poor prognosis is associated with an increased abundance of tumor-associated microglia and macrophages (TAMs), which are known to play a role in creating a pro-tumorigenic environment and aiding tumor progression. Most treatment strategies are directed against glioblastoma cells; however, accumulating evidence suggests targeting of TAMs as a promising therapeutic strategy. While TAMs are typically dichotomously classified as M1 and M2 phenotypes, recent studies utilizing single cell technologies have identified expression pattern differences, which is beginning to give a deeper understanding of the heterogeneous subpopulations of TAMs in glioblastomas. In this review, we evaluate the role of TAMs in the glioblastoma microenvironment and discuss how their interactions with cancer cells have an extensive impact on glioblastoma progression and treatment resistance. Finally, we summarize the effects and challenges of therapeutic strategies, which specifically aim to target TAMs.

AB - Glioblastoma is the most frequent and malignant primary brain tumor. Standard of care includes surgery followed by radiation and temozolomide chemotherapy. Despite treatment, patients have a poor prognosis with a median survival of less than 15 months. The poor prognosis is associated with an increased abundance of tumor-associated microglia and macrophages (TAMs), which are known to play a role in creating a pro-tumorigenic environment and aiding tumor progression. Most treatment strategies are directed against glioblastoma cells; however, accumulating evidence suggests targeting of TAMs as a promising therapeutic strategy. While TAMs are typically dichotomously classified as M1 and M2 phenotypes, recent studies utilizing single cell technologies have identified expression pattern differences, which is beginning to give a deeper understanding of the heterogeneous subpopulations of TAMs in glioblastomas. In this review, we evaluate the role of TAMs in the glioblastoma microenvironment and discuss how their interactions with cancer cells have an extensive impact on glioblastoma progression and treatment resistance. Finally, we summarize the effects and challenges of therapeutic strategies, which specifically aim to target TAMs.

KW - Crosstalk

KW - Glioblastoma

KW - Microenvironment

KW - TAM

KW - Therapeutic strategies

KW - Tumor-associated microglia and macrophages

U2 - 10.3390/cancers13174255

DO - 10.3390/cancers13174255

M3 - Review

C2 - 34503065

AN - SCOPUS:85113739126

VL - 13

JO - Cancers

JF - Cancers

SN - 2072-6694

IS - 17

M1 - 4255

ER -