دورية أكاديمية
أعرض في EDS

Cytokine responsiveness of CD8(+) T cells is a reproducible biomarker for the clinical efficacy of dendritic cell vaccination in glioblastoma patients.

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; Departments of Neurosurgery, University of California Los Angeles, Los Angeles, CA 90095, USA., Jin RM; Departments of Neurosurgery, University of California Los Angeles, Los Angeles, CA 90095, USA., Wang X; Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA., Safaee M; Departments of Neurosurgery, University of California Los Angeles, Los Angeles, CA 90095, USA., Scharnweber R; Departments of Neurosurgery, University of California Los Angeles, Los Angeles, CA 90095, USA., Lisiero DN; Departments of Neurosurgery, University of California Los Angeles, Los Angeles, CA 90095, USA.; Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, CA 90095, USA., Soto H; Departments of Neurosurgery, University of California Los Angeles, Los Angeles, CA 90095, USA., Liau LM; Departments of Neurosurgery, University of California Los Angeles, Los Angeles, CA 90095, USA.; Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, CA 90095, USA.; Brain Research Institute, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, CA 90095, USA., Prins RM; Departments of Neurosurgery, University of California Los Angeles, Los Angeles, CA 90095, USA.; Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, CA 90095, USA.; Brain Research Institute, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, CA 90095, USA.; Molecular and Medical Pharmacology, University of California Los Angeles, Los Angeles, CA 90095, USA.
المصدر: Journal for immunotherapy of cancer [J Immunother Cancer] 2014 May 13; Vol. 2, pp. 10. Date of Electronic Publication: 2014 May 13 (Print Publication: 2014).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: BMJ Publishing Group Ltd Country of Publication: England NLM ID: 101620585 Publication Model: eCollection Cited Medium: Print ISSN: 2051-1426 (Print) Linking ISSN: 20511426 NLM ISO Abbreviation: J Immunother Cancer Subsets: PubMed not MEDLINE
أسماء مطبوعة: Publication: 2020- : London, United Kingdom : BMJ Publishing Group Ltd.
Original Publication: London : BioMed Central, 2013-
مستخلص: 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.
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معلومات مُعتمدة: P30 CA016042 United States CA NCI NIH HHS; R25 NS079198 United States NS NINDS NIH HHS; UL1 TR000124 United States TR NCATS NIH HHS
فهرسة مساهمة: Keywords: Dendritic cells; Glioblastoma; Phospho-flow cytometry; T cells; Tumor immunity; pSTAT-5
تواريخ الأحداث: Date Created: 20140603 Date Completed: 20140602 Latest Revision: 20211021
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC4039989
DOI: 10.1186/2051-1426-2-10
PMID: 24883189
قاعدة البيانات: MEDLINE
الوصف
تدمد:2051-1426
DOI:10.1186/2051-1426-2-10