The Survival Benefit of Postoperative Bacterial Infections in Patients With Glioblastoma Multiforme: Myth or Reality?

Abstract

Glioblastoma multiforme (GBM), the most common malignant brain tumor, universally carries a poor prognosis. Despite aggressive multimodality treatment, the median survival is ~18-20 months, depending on molecular subgroups. A long history of observations suggests antitumor effects of bacterial infections against malignant tumors. The present review summarizes and critically analyzes the clinical data providing evidence for or against the survival benefit of post-operative bacterial infections in GBM patients. Furthermore, we explore the probable underlying mechanism(s) from basic science studies on the topic. There are plausible explanations from immunobiology for the mechanism of the "favorable effect" of bacterial infections in GBM patients. However, available clinical literature does not provide a definitive association between postoperative bacterial infection and prolonged survival in GBM patients. The presently available, single-/multi-center and national database retrospective case-control studies on the topic provide conflicting results. A prospective randomized study on the subject is clearly not possible. Immunobiology literature supports development of genetically modified bacteria as part of multimodal regimen against GBM.

Keywords: bacterial infections; glioblastoma multiforme; immune response; mechanism(s); survival benefit.

Figure 1

Schematic of mechanisms implicated in potential survival benefit of bacterial infections in GBM. Several theories have been proposed to explain how bacterial infection could lead to improved survival in GBM patients. One theory suggests that bacteria employ immune-evasion techniques such as sequestration of protein products and nutrients such as iron that are vital to sustain the vasculature and immense metabolic demands of neoplastic cells. Another theory is that bacterial infection within or near the tumor bed may stimulate the patient's immune response, thus resulting in an endogenous immune targeting against glioma cells. A biological argument that encompasses the ability of bacterial infections to induce augmented immunostimulatory response and to evoke a cascade of cytokines and chemokines, some of which also exert anticancer effects, has also been put forth.