Understanding the glioblastoma tumor microenvironment: leveraging the extracellular matrix to increase immunotherapy efficacy

Abstract

Glioblastoma (GBM) accounts for approximately half of all malignant brain tumors, and it remains lethal with a five-year survival of less than 10%. Despite the immense advancements in the field, it has managed to evade even the most promising therapeutics: immunotherapies. The main reason is the highly spatiotemporally heterogeneous and immunosuppressive GBM tumor microenvironment (TME). Accounting for this complex interplay of TME-driven immunosuppression is key to developing effective therapeutics. This review will explore the immunomodulatory role of the extracellular matrix (ECM) by establishing its contribution to the TME as a key mediator of immune responses in GBM. This relationship will help us elucidate therapeutic targets that can be leveraged to develop and deliver more effective immunotherapies.

Keywords: cancer-associated fibroblasts; collagen; decorin; extracellular matrix; fibronectin; glioblastoma; immunotherapy; tumor microenvironment.

Figure 1

From a cohort of 19 newly-diagnosed GBM patient tumor samples, immunohistochemical stains to fibronectin-1 and decorin were obtained. Per review by a board-certified pathologist, fibronectin was enhanced in areas immediately adjacent to necrosis, while decorin was enhanced within the necrotic core of the tumor. Presented here are three representative samples. Samples were collected by the The Nervous System Tumor Bank at Northwestern University was used to collect all human samples under IRB number STU00202003.

Figure 2

Illustration of representative findings of immunohistochemical stains for fibronectin-1 and decorin within a cohort of 19 newly diagnosed GBM tumor patient samples.