دورية أكاديمية
Cytokine responsiveness of CD8(+) T cells is a reproducible biomarker for the clinical efficacy of dendritic cell vaccination in glioblastoma patients.
العنوان: | Cytokine responsiveness of CD8(+) T cells is a reproducible biomarker for the clinical efficacy of dendritic cell vaccination in glioblastoma patients. |
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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. |
References: | Pediatr Blood Cancer. 2010 Apr;54(4):519-25. (PMID: 19852061) J Immunol. 2005 Aug 15;175(4):2366-73. (PMID: 16081807) N Engl J Med. 2010 Aug 19;363(8):711-23. (PMID: 20525992) Stem Cells. 1999;17(3):138-46. (PMID: 10342556) J Clin Neurosci. 2008 Feb;15(2):114-21. (PMID: 18083572) PLoS Med. 2007 May;4(5):e176. (PMID: 17488182) N Engl J Med. 2013 Jul 11;369(2):134-44. (PMID: 23724846) Clin Cancer Res. 2011 Mar 15;17(6):1603-15. (PMID: 21135147) Expert Rev Vaccines. 2010 Jun;9(6):631-43. (PMID: 20518718) J Clin Neurosci. 2011 Aug;18(8):1048-54. (PMID: 21715171) Am J Health Syst Pharm. 2011 May 1;68(9):768. (PMID: 21515855) Cancer Res. 2008 Jul 15;68(14):5955-64. (PMID: 18632651) Cytometry A. 2013 Aug;83(8):728-38. (PMID: 23788464) Nat Rev Cancer. 2008 Apr;8(4):299-308. (PMID: 18354418) Clin Cancer Res. 2005 Aug 1;11(15):5515-25. (PMID: 16061868) Neuro Oncol. 2012 Sep;14(9):1178-84. (PMID: 22869622) Semin Immunol. 2008 Oct;20(5):286-95. (PMID: 18951039) World Neurosurg. 2012 May-Jun;77(5-6):736-44. (PMID: 22120301) Clin Cancer Res. 2009 Jun 15;15(12):4085-94. (PMID: 19509154) Lancet Oncol. 2009 May;10(5):459-66. (PMID: 19269895) J Exp Med. 2005 Apr 18;201(8):1257-68. (PMID: 15824085) Immunity. 1999 Feb;10(2):249-59. (PMID: 10072077) Clin Dev Immunol. 2011;2011:732413. (PMID: 22190972) Br J Cancer. 2004 Nov 1;91(9):1656-62. (PMID: 15477864) Clin Cancer Res. 2005 Jun 1;11(11):4160-7. (PMID: 15930352) J Leukoc Biol. 2014 Jan;95(1):33-46. (PMID: 23924658) PLoS One. 2012;7(4):e32614. (PMID: 22485134) Cancer Immunol Immunother. 2013 Jan;62(1):125-35. (PMID: 22847020) Cancer Immunol Immunother. 2012 Nov;61(11):2033-44. (PMID: 22527250) Cell Biochem Biophys. 2012 Jan;62(1):91-9. (PMID: 21909820) J Neurooncol. 2010 Sep;99(2):261-72. (PMID: 20146084) J Clin Oncol. 2011 Jan 20;29(3):330-6. (PMID: 21149657) J Immunother. 2011 May;34(4):382-9. (PMID: 21499132) Front Oncol. 2013 May 06;3:109. (PMID: 23653893) Clin Cancer Res. 2008 May 15;14(10):3098-104. (PMID: 18483377) J Immunol. 2006 Jan 1;176(1):157-64. (PMID: 16365406) Clin Cancer Res. 2006 Oct 1;12(19):5850-8. (PMID: 17020993) Bull Exp Biol Med. 2007 Apr;143(4):528-34. (PMID: 18214316) Neurosurg Focus. 2000 Dec 15;9(6):e8. (PMID: 16817691) J Immunol. 2005 Jun 1;174(11):6791-802. (PMID: 15905520) Mol Cancer Ther. 2009 Oct;8(10):2773-9. (PMID: 19825799) J Immunol. 2011 May 1;186(9):5068-77. (PMID: 21430221) Blood. 2006 Jan 15;107(2):602-9. (PMID: 16150945) Adv Exp Med Biol. 2012;746:53-76. (PMID: 22639159) J Clin Neurosci. 2013 May;20(5):670-5. (PMID: 23352352) J Immunother. 2013 Feb;36(2):152-7. (PMID: 23377664) Trends Genet. 1995 Feb;11(2):69-74. (PMID: 7716810) Clin Cancer Res. 2011 Jun 1;17(11):3520-6. (PMID: 21471425) N Engl J Med. 2005 Mar 10;352(10):987-96. (PMID: 15758009) J Neurosurg. 1999 Jun;90(6):1115-24. (PMID: 10350260) Oncoimmunology. 2013 Aug 1;2(8):e26012. (PMID: 24083085) Cancer Res. 2003 May 15;63(10):2535-45. (PMID: 12750277) |
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 |
تدمد: | 2051-1426 |
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DOI: | 10.1186/2051-1426-2-10 |