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Review Article

Chronic inflammation drives glioma growth:

cellular and molecular factors responsible for an

immunosuppressive microenvironment

Edward T. Ha , Joseph P. Antonios , Horacio Soto , Robert M. Prins 1,3,4 , Isaac Yang , Noriyuki Kasahara ,
1
2
1
1,4
1
Linda M. Liau 1,3,4 , Carol A. Kruse 1,3,4
1 Department of Neurosurgery, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
2 Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
3 Brain Research Institute, University of California, Los Angeles, CA 90095, USA.
4 Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA 90095, USA.
ABSTRA CT

This review examines glioma disease initiation, promotion, and progression with a focus on the cell types present within the tumor mass
and the molecules responsible for the immunosuppressive microenvironment that are present at each step of the disease. The cell
types and molecules present also correlate with the grade of malignancy. An overall “type 2” chronic inflammatory microenvironment
develops that facilitates glioma promotion and contributes to the neo‑vascularization characteristic of gliomas. An immunosuppressive
microenvironment shields the tumor mass from clearance by the patient’s own immune system. Here, we provide suggestions to
deal with a chronically‑inflamed tumor microenvironment and provide recommendations to help optimize adjuvant immune‑ and
gene therapies currently offered to glioma patients.

Key words: Astrocytoma, glioma, immunotherapy, inflammation, microenvironment

INTRODUCTION actively pursued. While immunotherapies seemingly
provide viable, theoretically effective options, in
The World Health Organization (WHO) grade IV practice they have produced mixed results. The glioma
glioma is called glioblastoma, and is formerly termed microenvironment is highly immunosuppressive,
glioblastoma multiforme (GBM) because its appearance thereby inhibiting the efficacy of immune treatments.
can take on a variety of morphologic forms. GBM is Microenvironmental factors allow glioma cell evasion
the most common and lethal of all primary malignant from the immune system. The source of the factors is
brain tumors, and is responsible for over 13,000 not solely derived from the tumor mass, but rather is
deaths per year in the United States. The median also a consequence of chronic inflammation present
[1]
survival is approximately 15 months. The first in the tumor microenvironment.
[2]
line of treatment for this disease is usually surgical
resection followed by concurrent chemo-radiotherapy. GLIOMAS AND CHRONIC INFLAMMATION
Importantly, the invasive tumor cells that remain
after surgery and survive these aggressive treatments Chronic inflammation can influence a wide range
are likely responsible for tumor recurrence. Thus, of ailments including heart disease, stroke, Crohn’s
alternative novel therapies that enhance or work in disease, rheumatoid arthritis, multiple sclerosis, asthma,
conjunction with conventional treatments are being Alzheimer’s, depression, fatigue, neuropathic pain,
and - relevant to our discussion - cancer. [3-13] Indeed,
Access this article online it is thought that around 15% of all cancer-related
Quick Response Code: deaths are in some form linked with inflammation as a
Website: result of bacterial or viral infections. [14] Further, chronic
www.nnjournal.net
inflammation occurring within the microenvironment
DOI: of tumor lesions is now thought to either drive the first
10.4103/2347-8659.139717 malignant-conferring genetic mutations and/or induce
them as a result of oncogene expression. [14]

Corresponding Author: Carol A. Kruse, Department of Neurosurgery, David Geffen School of Medicine, University of
California, Gonda Center, Box 951761, MC 176122, 695 Charles E Young Drive South, Los Angeles, CA 90095, USA.
Email: ckruse@mednet.ucla.edu

66 Neuroimmunol Neuroinflammation | Volume 1 | Issue 2 | September 2014