Long-term Remission of Malignant Brain Tumors after Intracranial Infection: A Report of Four Cases

Bowles, Alfred P.; Perkins, Eddie

doi:10.1097/00006123-199903000-00110

Cited by 57 publications

(31 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In some tumor types, Th1 cells are tumoricidal via a FasL-Fas interaction, while Th2 cells promote tumor growth [22], underscoring the ability of the two helper T cell types to exert opposite effects on tumors. The observations that glioblastoma patients who experience postoperative cranial wound infections exhibit longer survival [23,24] and that postoperative empyema prolongs survival in bronchogenic carcinoma patients [25,26] have been attributed to bacterial lipopolysaccharide (LPS) eliciting a nonspecific immune response a portion of which targets the tumor [27,28] or to these infections causing an immune cell infiltrate at the tumor resection site which promotes a specific cross-reactive immunological attack against the tumor. However, our findings also raise the possibility that tumor mutations might stratify patients into two groups with different circulating helper T cell profiles-those with more potent antitumor Th1-mediated cellular immunity capable of limiting tumor growth may also have weaker Th2-mediated humoral immunity rendering them more prone to infections, while patients whose tumor mutations lead to a circulating Th2 profile might ward off infection effectively but be unable to mount a cellular immune response against the tumor.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2009

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 99%

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

et al. 2009

View full text Add to dashboard Cite

show abstract

“…Of note, the longest overall survivor in this group (991 days) suffered from postoperative intracranial abscess requiring multiple surgical procedures for drainage. Intracranial infections in malignant glioma patients are associated with prolonged survival and have been proposed to initiate an antitumor immune response (22).…”

Section: Methodsmentioning

confidence: 99%

Clinical Responsiveness of Glioblastoma Multiforme to Chemotherapy after Vaccination

Wheeler

Das

Liu

et al. 2004

Clinical Cancer Research

240

157

View full text Add to dashboard Cite

Purpose: Although the development of immune-based therapies for various cancers including malignant glioma has been heralded with much hope and optimism, objective clinical improvements in most vaccinated cancer patients have not been realized. To broaden the search for vaccineinduced benefits, we examined synergy of vaccines with conventional chemotherapy.Experimental Design: Survival and progression times were analyzed retrospectively in 25 vaccinated (13 with and 12 without subsequent chemotherapy) and 13 nonvaccinated de novo glioblastoma (GBM) patients receiving chemotherapy. Immune responsiveness and T-cell receptor excision circle (TREC) content within CD8 ؉ T cells (CD8 ؉ TRECs) was determined in vaccinated patients.Results: Vaccinated patients receiving subsequent chemotherapy exhibited significantly longer times to tumor recurrence after chemotherapy relative to their own previous recurrence times, as well as significantly longer postchemotherapy recurrence times and survival relative to patients receiving isolated vaccination or chemotherapy. Patients exhibiting objective (>50%) tumor regression, extremely rare in de novo GBM, were also confined to the vaccine ؉ chemotherapy group. Prior tumor behavior, demographic factors, other treatment variables, distribution of vaccine responders, and patients with high CD8 ؉ TRECs all failed to account for these differences in clinical outcome. Within all GBM patients receiving post-vaccine chemotherapy, however, CD8؉ TRECs predicted significantly longer chemotherapeutic responses, revealing a strong link between the predominant T-cell effectors in GBM and tumor chemosensitivity. Conclusions:We propose that therapeutic vaccination synergizes with subsequent chemotherapy to elicit tangible clinical benefits for GBM patients.

show abstract

“…Any of these changes in proteins expressed by tumors can be sufficient for the immune system to recognize specifically proteins expressed by tumors as antigenic, and mount an immune response against these proteins. There is some anecdotal evidence in the literature of spontaneous regression of skin tumors, or even brain tumors following infection, and it is believed that the immune system can mediate tumor rejection in these cases [9][10][11]. However, this is not a common event and tumors secrete many antiinflammatory mediators and other proteins that can stifle the development of an effective antitumor response.…”

Section: Immune Based Gene Therapies For Gbmmentioning

confidence: 99%

Combining Cytotoxic and Immune-Mediated Gene Therapy to Treat Brain Tumors

Curtin

King

Candolfi

et al. 2005

CTMC

View full text Add to dashboard Cite

Glioblastoma (GBM) is a type of intracranial brain tumor, for which there is no cure. In spite of advances in surgery, chemotherapy and radiotherapy, patients die within a year of diagnosis. Therefore, there is a critical need to develop novel therapeutic approaches for this disease. Gene therapy, which is the use of genes or other nucleic acids as drugs, is a powerful new treatment strategy which can be developed to treat GBM. Several treatment modalities are amenable for gene therapy implementation, e.g. conditional cytotoxic approaches, targeted delivery of toxins into the tumor mass, immune stimulatory strategies, and these will all be the focus of this review.Both conditional cytotoxicity and targeted toxin mediated tumor death, are aimed at eliminating an established tumor mass and preventing further growth. Tumors employ several defensive strategies that suppress and inhibit anti-tumor immune responses. A better understanding of the mechanisms involved in eliciting anti-tumor immune responses has identified promising targets for immunotherapy. Immunotherapy is designed to aid the immune system to recognize and destroy tumor cells in order to eliminate the tumor burden. Also, immune-therapeutic strategies have the added advantage that an activated immune system has the capability of recognizing tumor cells at distant sites from the primary tumor, therefore targeting metastasis distant from the primary tumor locale. Pre-clinical models and clinical trials have demonstrated that in spite of their location within the central nervous system (CNS), a tissue described as 'immune privileged', brain tumors can be effectively targeted by the activated immune system following various immunotherapeutic strategies. This review will highlight recent advances in brain tumor immunotherapy, with particular emphasis on advances made using gene therapy strategies, as well as reviewing other novel therapies that can be used in combination with immunotherapy. Another important aspect of implementing gene therapy in the clinical arena is to be able to image the targeting of the therapeutics to the tumors, treatment effectiveness and progression of disease. We have therefore reviewed the most exciting non-invasive, in vivo imaging techniques which can be used in combination with gene therapy to monitor therapeutic efficacy over time.

show abstract

Long-term Remission of Malignant Brain Tumors after Intracranial Infection: A Report of Four Cases

Abstract: The case histories presented in conjunction with the relevant literature reviewed support the concept that microbial infections may influence immune responses in brain tumor defense.

Cited by 57 publications

References 28 publications

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

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

Clinical Responsiveness of Glioblastoma Multiforme to Chemotherapy after Vaccination

Combining Cytotoxic and Immune-Mediated Gene Therapy to Treat Brain Tumors

Contact Info

Product

Resources

About