Decreased rate of infection in glioblastoma patients with allelic loss of chromosome 10q.
BACKGROUND
Chromosome 10q allelic loss commonly occurs in glioblastoma. Disruption of PTEN, one of three known 10q tumor suppressor genes, affects the immune system by increasing tumor expression of immunosuppressive protein B7-H1 and by increasing tumor release of Th2-inducing cytokines. While the former might impair antitumor cellular immunity, a consideration for immunotherapy, the latter could cause 10q-maintaining tumor patients to experience comparatively higher rates of bacterial infections, a source of morbidity and mortality in glioblastoma patients.


METHODS
We retrospectively reviewed 58 glioblastoma patients whose tumors were designated "normal-10q" (n = 16) or "LOH-10q" (n = 42) using loss of heterozygosity (LOH) assays of microsatellite markers in constitutional/tumor DNA pairs. Records were reviewed for symptomatic, microbiologically or radiographically confirmed infections in the first 2 years after diagnosis.


RESULTS
Infection occurred more frequently in "normal-10q" than "LOH-10q" patients (56% vs. 14% of patients experiencing infection; P = 0.001). "Normal-10q" patients more commonly developed all four infection types studied (urinary tract = 38% vs. 13%, craniotomy wound = 19% vs. 0%, pneumonia = 19% vs. 5%, sepsis = 6% vs. 3%). "Normal-10q" and "LOH-10q" patients had similar survival, ages, chemotherapy treatment rates, and frequency of patients on dexamethasone 1 month after radiation therapy (P = 0.4-0.98), making these factors unlikely to explain the observed difference in infection rates.


CONCLUSIONS
While tumor mutations may inhibit antitumor immunity, the effects of these mutations on systemic immunity remain undetermined. We found higher infection rates after glioblastoma diagnosis in patients whose tumors maintained chromosome 10q than in patients whose tumors had allelic 10q loss. Differing effects of this genetic alteration on antitumor and systemic immunity may warrant further investigation, potentially providing insight into mechanisms of antitumor immunity and host defenses against local and systemic infections.
Aghi
Manish K
MK
Department of Neurological Surgery, University of California at San Francisco (UCSF), San Francisco, CA 94143-0112, USA. AghiM@neurosurg.ucsf.edu
Batchelor
Tracy T
TT
Louis
David N
DN
Barker
Fred G
FG
Curry
William T
WT
D001424:Bacterial Infections / Q000235:genetics*; D001932:Brain Neoplasms / Q000150:complications / Q000235:genetics* / Q000401:mortality; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics*; D005909:Glioblastoma / Q000150:complications / Q000235:genetics* / Q000401:mortality; D006801:Humans; D053208:Kaplan-Meier Estimate; D019656:Loss of Heterozygosity / Q000235:genetics*; D008875:Middle Aged; D012189:Retrospective Studies