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. 2021 Nov 27;3(Suppl 5):v121-v132.
doi: 10.1093/noajnl/vdab121. eCollection 2021 Nov.

The microenvironment of brain metastases from solid tumors

Ethan S Srinivasan  1 , Krutika Deshpande  2 , Josh Neman  3 , Frank Winkler  4   5 , Mustafa Khasraw  1
Affiliations

The microenvironment of brain metastases from solid tumors

Ethan S Srinivasan et al. Neurooncol Adv. .

Abstract

Brain metastasis (BrM) is an area of unmet medical need that poses unique therapeutic challenges and heralds a dismal prognosis. The intracranial tumor microenvironment (TME) presents several challenges, including the therapy-resistant blood-brain barrier, a unique immune milieu, distinct intercellular interactions, and specific metabolic conditions, that are responsible for treatment failures and poor clinical outcomes. There is a complex interplay between malignant cells that metastasize to the central nervous system (CNS) and the native TME. Cancer cells take advantage of vascular, neuronal, immune, and anatomical vulnerabilities to proliferate with mechanisms specific to the CNS. In this review, we discuss unique aspects of the TME in the context of brain metastases and pathways through which the TME may hold the key to the discovery of new and effective therapies for patients with BrM.

Keywords: brain metastasis; immune suppression; microenvironment; neural niche; therapeutic targets.

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Figures

Figure 1.
Figure 1.
Diagram depicting blood–brain barrier organization and platelet-supported arrest of circulating tumor cell within the cerebral microvasculature. The figure was created with biorender.com.
Figure 2.
Figure 2.
(A) Diagram depicting vascular co-option and VEGF-mediated angiogenesis within the perivascular niche of the tumor microenvironment. (B) Summary of major interactions within the tumor microenvironment of brain metastases between tumor cells, tumor-associated macrophages, reactive astrocytes, neurons, and tumor-infiltrating lymphocytes. The figure was created with biorender.com.
See this image and copyright information in PMC

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