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.

Prolonged survival in patients with local chronic infection after high-grade glioma treatment: Two case reports

“…One of the potential activators of the immune response may also be a bacterial infection. It was found that bacterial-based tumor therapy inhibits tumor cell growth in different cancer types, like sarcomas or superficial bladder cancer (5,6). Here we present two case reports of unexpectedly long survival in patients with chronic and prolonged bacterial infection at the site of craniotomy after standard therapy of HGG.…”

“…Another proposed mechanism is the stimulation patient's immune response within or near the tumor bed while avoiding the systemic response (6,11). It is well known that GBM induces tumor-associated immune suppression both within its microenvironment as well as systematically (20).…”

“…Several theories have been proposed to explain how bacteria affect the microenvironment around the GBM cells. One of the possible mechanisms is the sequestration of nutrients needed for bacterial cells leading to a limitation of resources for the high metabolic demands of GBM cells (6).…”

Surgical site infections after glioblastoma surgery: boon or bane?

“…In brain tumors, SSIs have been reported to occur in 4–8% of the surgeries (Scheer et al 2023 ; Uzuka et al 2017 ). For a long time, it has been hypothesized that bacterial SSIs might positively affect survival time in cancer patients (Kazim et al 2021 ; Nauts 1989 ). In the late nineteenth and early twentieth century, the orthopedic surgeon and cancer researcher William B. Coley even inoculated bacterial organisms (Coley's toxins) into more than 1000 patients with inoperable cancer and reported an “anti-cancer effect” of bacterial infections (Coley 1898 , 1991 ; McCarthy 2006 ).…”

Interaction between Bacteria and the Immune System for Cancer Immunotherapy: The α-GalCer Alliance

“…In pancreatic cancer, and in contrast to normal pancreatic tissue, bacteria and fungi colonize the cancerous tissues, affecting the response and prognosis to treatment [ 15 ]. Interestingly, bacterial infection within or near the tumor bed has also been suggested to stimulate patients’ immune responses in brain tumors, for example, in glioblastoma (GBM) patients [ 16 ].…”