Tumor-Associated Microglia and Macrophages in the Glioblastoma Microenvironment and Their Implications for Therapy

Andersen, Rikke; Anand, Atul; Harwood, Dylan Scott Lykke; Kristensen, Bjarne Winther

doi:10.3390/cancers13174255

Cited by 76 publications

(69 citation statements)

References 186 publications

(247 reference statements)

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“…Indeed, GBM cells recruit microglia and macrophages in the TME by means of chemoattractants (e.g., C-C motif chemokine ligand 2 (CCL2), CSF-1) [ 69 , 70 ] and induce a switch to pro-tumoral subtype [ 65 , 71 , 72 ]. In return, TAMs promote tumor cell proliferation and angiogenesis as well as inhibition of effector T cells proliferation and attraction of T regulatory cells (Tregs) and MDSCs through cytokines secretion [ 65 , 72 , 73 ].…”

Section: The Bbb and Immune Microenvironment In Gbm: Implications For The Development Of New Therapiesmentioning

confidence: 99%

Immunotherapy for glioblastoma: the promise of combination strategies

Bausart

Préat

Malfanti

2022

J Exp Clin Cancer Res

129

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Glioblastoma (GBM) treatment has remained almost unchanged for more than 20 years. The current standard of care involves surgical resection (if possible) followed by concomitant radiotherapy and chemotherapy. In recent years, immunotherapy strategies have revolutionized the treatment of many cancers, increasing the hope for GBM therapy. However, mostly due to the high, multifactorial immunosuppression occurring in the microenvironment, the poor knowledge of the neuroimmune system and the presence of the blood−brain barrier, the efficacy of immunotherapy in GBM is still low. Recently, new strategies for GBM treatments have employed immunotherapy combinations and have provided encouraging results in both preclinical and clinical studies. The lessons learned from clinical trials highlight the importance of tackling different arms of immunity. In this review, we aim to summarize the preclinical evidence regarding combination immunotherapy in terms of immune and survival benefits for GBM management. The outcomes of recent studies assessing the combination of different classes of immunotherapeutic agents (e.g., immune checkpoint blockade and vaccines) will be discussed. Finally, future strategies to ameliorate the efficacy of immunotherapy and facilitate clinical translation will be provided to address the unmet medical needs of GBM.

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Section: The Bbb and Immune Microenvironment In Gbm: Implications For The Development Of New Therapiesmentioning

confidence: 99%

Immunotherapy for glioblastoma: the promise of combination strategies

Bausart

Préat

Malfanti

2022

J Exp Clin Cancer Res

129

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“…Particularly, tumor-associated macrophages (TAMs) are the dominant infiltrating immune cell population [32]. TAMs display a heterogeneous spectrum of phenotypes, of which extremes exert either antitumor (M1-like) or protumor functions (M2-like) [33].…”

Section: Heterogeneity Of Gbmmentioning

confidence: 99%

Advancements, Challenges, and Future Directions in Tackling Glioblastoma Resistance to Small Kinase Inhibitors

Fabro

Lamfers

Leenstra

2022

Cancers

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Despite clinical intervention, glioblastoma (GBM) remains the deadliest brain tumor in adults. Its incurability is partly related to the establishment of drug resistance, both to standard and novel treatments. In fact, even though small kinase inhibitors have changed the standard clinical practice for several solid cancers, in GBM, they did not fulfill this promise. Drug resistance is thought to arise from the heterogeneity of GBM, which leads the development of several different mechanisms. A better understanding of the evolution and characteristics of drug resistance is of utmost importance to improve the current clinical practice. Therefore, the development of clinically relevant preclinical in vitro models which allow careful dissection of these processes is crucial to gain insights that can be translated to improved therapeutic approaches. In this review, we first discuss the heterogeneity of GBM, which is reflected in the development of several resistance mechanisms. In particular, we address the potential role of drug resistance mechanisms in the failure of small kinase inhibitors in clinical trials. Finally, we discuss strategies to overcome therapy resistance, particularly focusing on the importance of developing in vitro models, and the possible approaches that could be applied to the clinic to manage drug resistance.

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“… On the left, an illustration of the different cell populations composing glioblastoma and its microenvironment, as well as associated blood-brain barrier disruption. On the right, a summary of the different areas covered by the articles in this Special Issue: GBM cells, stem cells, and preclinical studies [ 2 , 3 , 4 , 5 , 6 ], clinical studies [ 7 , 8 ], immunotherapy and new treatments [ 9 , 10 , 11 , 12 ]. Created with BioRender.com.…”

Section: Figurementioning

confidence: 99%

“…Eleven papers are included in this issue [ 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 ], and they range from in vitro and preclinical studies to clinical studies, and to immunotherapy and new potential treatments for glioblastomas ( Figure 1 ).…”

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confidence: 99%

“…Andersen et al reviewed the role of tumor-associated macrophages (TAMs) in the GBM microenvironment [ 10 ]. While TAMs have been classified as M1 and M2 phenotypes, recent studies based on single-cell technologies have identified expression pattern differences; the results of these studies are beginning to provide us with a deeper understanding of the heterogeneous subpopulations of TAMs in glioblastomas.…”

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confidence: 99%

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