التفاصيل البيبلوغرافية
العنوان:
Cytokine responsiveness of CD8+T cells is a reproducible biomarker for the clinical efficacy of dendritic cell vaccination in glioblastoma patients
المؤلفون:
Everson, RG , Jin, RM , Wang, X , Safaee, M , Scharnweber, R , Lisiero, DN , Soto, H , Liau, LM , Prins, RM
المصدر:
Everson, RG; Jin, RM; Wang, X; Safaee, M; Scharnweber, R; Lisiero, DN; et al.(2014). Cytokine responsiveness of CD8+T cells is a reproducible biomarker for the clinical efficacy of dendritic cell vaccination in glioblastoma patients. Journal for ImmunoTherapy of Cancer, 2(1), 10. doi: 10.1186/2051-1426-2-10. UCLA: Retrieved from: http://www.escholarship.org/uc/item/1gp6z10p
بيانات النشر:
eScholarship, University of California, 2014.
سنة النشر:
2014
الوصف:
© 2014 Everson et al.; licensee BioMed Central Ltd. Background: Immunotherapeutic approaches, such as dendritic cell (DC) vaccination, have emerged as promising strategies in the treatment of glioblastoma. Despite their promise, however, the absence of objective biomarkers and/or immunological monitoring techniques to assess the clinical efficacy of immunotherapy still remains a primary limitation. To address this, we sought to identify a functional biomarker for anti-tumor immune responsiveness associated with extended survival in glioblastoma patients undergoing DC vaccination.Methods: 28 patients were enrolled and treated in two different Phase 1 DC vaccination clinical trials at UCLA. To assess the anti-tumor immune response elicited by therapy, we studied the functional responsiveness of pre- and post-vaccination peripheral blood lymphocytes (PBLs) to the immunostimulatory cytokines interferon-gamma (IFN-γ) and interleukin-2 (IL-2) in 21 of these patients for whom we had adequate material. Immune responsiveness was quantified by measuring downstream phosphorylation events of the transcription factors, STAT-1 and STAT-5, via phospho-specific flow cytometry.Results: DC vaccination induced a significant decrease in the half-maximal concentration (EC-50) of IL-2 required to upregulate pSTAT-5 specifically in CD3+CD8+T lymphocytes (p < 0.045). Extended survival was also associated with an increased per cell phosphorylation of STAT-5 in cytotoxic T-cells following IL-2 stimulation when the median post/pre pSTAT-5 ratio was used to dichotomize the patients (p = 0.0015, log-rank survival; hazard ratio = 0.1834, p = 0.018). Patients whose survival was longer than two years had a significantly greater pSTAT-5 ratio (p = 0.015), but, contrary to our expectations, a significantly lower pSTAT-1 ratio (p = 0.038).Conclusions: Our results suggest that monitoring the pSTAT signaling changes in PBL may provide a functional immune monitoring measure predictive of clinical efficacy in DC-vaccinated patients.
وصف الملف:
application/pdf
اللغة:
English
URL الوصول:
https://explore.openaire.eu/search/publication?articleId=od_______325::0f7390a4bad62870f21ac88e61433718 http://www.escholarship.org/uc/item/1gp6z10p
حقوق:
OPEN
رقم الأكسشن:
edsair.od.......325..0f7390a4bad62870f21ac88e61433718
قاعدة البيانات:
OpenAIRE
