Decreased rate of infection in glioblastoma patients with allelic loss of chromosome 10q

Abstract

Introduction 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%). ''Normal10q'' 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. Conclusion 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.

Common chromosomal aberrations detected by array comparative genomic hybridization in specialized stromal tumors of the prostate

“…18,19 Three tumor suppressor genes residing on chromosome 10q (ERCC6, PTEN/MMAC1, and DMBT1) have been implicated in the development and progression of several types of neoplasms. [20][21][22] High frequency of allelic loss on chromosome 10q23, where PTEN/MMAC1 gene locates was also reported in phyllodes tumor of the prostate. 8 No tumor suppressor genes have been well defined on chromosome 14, but putative tumor suppressor loci had been mapped by using microsatellite allotyping.…”

Immunological Aspects of Malignant Gliomas

“…The former relies on local cellular immunity mediated by the Th 1 subset of helper T cells, while the latter relies on systemic humoral immunity mediated by the Th 2 subset of helper T cells. [34][35] Past empiric observations reported that patients with GBM who experienced a postoperative cranial wound infection exhibited longer survival. This observation was initially attributed to bacterial lipopolysaccharide (LPS) eliciting a nonspecific immune response which also targets the tumor.…”

“…[40][41][42] The most common genetic alteration in GBM tumors is the loss of heterozygosity of chromosome #10, occurring in 80~95% of these tumors. [34][35][40][41][42] Interestingly, disruption of two of these tumor suppressor genes found on chromosome 10q may mediate a decrease in tumor cell immunogenicity (i.e. DBMT1, PTEN).…”

Can High Intensity Focused Ultrasound Facilitate Immunomodulation in Glioblastoma Multiforme?

“…Since these initial pivotal observations, with developing techniques and widespread interest, multiple studies were put forward describing different molecular immunosuppressive mechanisms taking place in GBM cells and microenvironment, claiming these to be the dominant key events (table 1) [1,5] . Unfortunately, things are not as straightforward or simple, and both arms of the immune system are known to be hampered in GBM, as do many other anatomical barriers, micro-environmental conditions and features unique to tumors within the central nervous system, once termed as immune-privileged [27][28] .…”