Fighting vessel dysmorphia to improve glioma chemotherapy

Abstract

High‐grade gliomas are aggressive and abundantly vascular tumors, and as in most cancer types, blood vessels in advanced lesions are highly abnormal. Poor perfusion and vascular leakage in tumor tissue resulting in hypoxia, necrosis, and high interstitial fluid pressure can hamper the efficient delivery of chemotherapy. Tumor angiogenesis is known to be supported by host leukocytes recruited to the tumor microenvironment, but the mechanisms leading to dysfunctional vascular network formation are incompletely understood. In this issue of EMBO Molecular Medicine, Mathivet et al (2017) present an elegant study, where longitudinal intravital imaging gives new insight on how recruitment and polarization of tumor‐associated macrophages regulate aberrant angiogenesis in experimental gliomas. They show that macrophage targeting results in vessel normalization and improved chemotherapy response, suggesting that the combination of these therapeutic modalities could improve the outcome of glioma treatment in the clinic.

Three-dimensional visualization of blood vessels in human gliomas based on tissue clearing and deep learning

“…High-grade gliomas, like most tumors, have a high degree of vascular heterogeneity in advanced lesions [25]. However, 2D based analysis methods suffer from structural overlap, particularly in highly heterogeneous gliomas, where paraffin sections separated by tens of micrtons can reflect different vascular characteristics, and even the structure of vessels in different sites of the same surface can vary considerably.…”

“…High-grade gliomas, like most tumors, have a high degree of vascular heterogeneity in advanced lesions [25] Since the diameter of blood vessels is closely related to the properties of hemodynamics, a larger vessel diameter implies less resistance to blood flow and a higher number of branches implies having a larger amount of neovascularization [44,45]. Accordingly, we might speculate that high-grade gliomas have a higher demand for blood than low-grade gliomas.…”