Tumor Microenvironment in Gliomas: A Treatment Hurdle or an Opportunity to Grab?

Author:

Di Nunno Vincenzo1,Aprile Marta2,Gatto Lidia1,Tosoni Alicia3,Ranieri Lucia3,Bartolini Stefania3,Franceschi Enrico3

Affiliation:

1. Department of Oncology, Azienda Unità Sanitaria Locale (AUSL) Bologna, 40139 Bologna, Italy

2. Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, 40136 Bologna, Italy

3. Nervous System Medical Oncology Department, IRCCS Istituto delle Scienze Neurologiche di Bologna, 40139 Bologna, Italy

Abstract

Gliomas are the most frequent central nervous system (CNS) primary tumors. The prognosis and clinical outcomes of these malignancies strongly diverge according to their molecular alterations and range from a few months to decades. The tumor-associated microenvironment involves all cells and connective tissues surrounding tumor cells. The composition of the microenvironment as well as the interactions with associated neoplastic mass, are both variables assuming an increasing interest in these last years. This is mainly because the microenvironment can mediate progression, invasion, dedifferentiation, resistance to treatment, and relapse of primary gliomas. In particular, the tumor microenvironment strongly diverges from isocitrate dehydrogenase (IDH) mutated and wild-type (wt) tumors. Indeed, IDH mutated gliomas often show a lower infiltration of immune cells with reduced angiogenesis as compared to IDH wt gliomas. On the other hand, IDH wt tumors exhibit a strong immune infiltration mediated by several cytokines and chemokines, including CCL2, CCL7, GDNF, CSF-1, GM-CSF, etc. The presence of several factors, including Sox2, Oct4, PD-L1, FAS-L, and TGF β2, also mediate an immune switch toward a regulatory inhibited immune system. Other important interactions are described between IDH wt glioblastoma cells and astrocytes, neurons, and stem cells, while these interactions are less elucidated in IDH-mutated tumors. The possibility of targeting the microenvironment is an intriguing perspective in terms of therapeutic drug development. In this review, we summarized available evidence related to the glioma microenvironment, focusing on differences within different glioma subtypes and on possible therapeutic development.

Funder

Italian Ministry of Health

Publisher

MDPI AG

Subject

Cancer Research,Oncology

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