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Serum HMGB1 is a predictive and prognostic biomarker for oncolytic immunotherapy
- Source :
- Oncoimmunology
- Publication Year :
- 2015
- Publisher :
- Informa UK Limited, 2015.
-
Abstract
- With the emergence of effective immunotherapeutics, which nevertheless harbor the potential for toxicity and are expensive to use, biomarkers are urgently needed for identification of cancer patients who respond to treatment. In this clinical-epidemiological study of 202 cancer patients treated with oncolytic adenoviruses, we address the biomarker value of serum high-mobility group box 1 (HMGB1) protein. Overall survival and imaging responses were studied as primary endpoints and adjusted for confounding factors in two multivariate analyses (Cox and logistic regression). Mechanistic studies included assessment of circulating tumor-specific T-cells by ELISPOT, virus replication by quantitative PCR, and inflammatory cytokines by cytometric bead array. Patients with low HMGB1 baseline levels (below median concentration) showed significantly improved survival (p = 0.008, Log-Rank test) and radiological disease control rate (49.2% vs. 30.0%, p = 0.038, χ2 test) as compared to high-baseline patients. In multivariate analyses, the low HMGB1 baseline status was a strong prognostic (HR 0.638, 95% CI 0.462–0.881) and the best predictive factor for disease control (OR 2.618, 95% CI 1.004–6.827). Indicative of an immune-mediated mechanism, antitumor T-cell activity in blood and response to immunogenic-transgene coding viruses associated with improved outcome only in HMGB1-low patients. Our results suggest that serum HMGB1 baseline is a useful prognostic and predictive biomarker for oncolytic immunotherapy with adenoviruses, setting the stage for prospective clinical studies.
- Subjects :
- Oncology
Oncolytic adenovirus
medicine.medical_specialty
medicine.medical_treatment
Immunology
03 medical and health sciences
0302 clinical medicine
Internal medicine
medicine
cancer
Immunology and Allergy
Author's View
030304 developmental biology
HMGB1
0303 health sciences
business.industry
ELISPOT
Confounding
predictive markers
Cancer
Immunotherapy
medicine.disease
oncolytic adenovirus
3. Good health
Oncolytic virus
tumor biomarkers
030220 oncology & carcinogenesis
Toxicity
ATAP, Advanced Therapy Access Program
CD40L, CD40-ligand
CI, confidence interval
CT, contrast-enhanced computed tomography
DAMP, damage-associated molecular pattern
GMCSF, granulocyte-macrophage colony stimulating factor
HMGB1, high-mobility group box 1
HR, hazard ratio
IL-6, -8, -10, interleukin-6, -8, -10
ILT2, immunoglobulin-like transcript 2
MRI, magnetic resonance imaging
OR, odds ratio
PET, positron emission tomography
RECIST, Response Evaluation Criteria In Solid Tumors
TNF-a, tumor-necrosis factor-α
WHO, World Health Organization
Biomarker (medicine)
immunotherapy
business
prognostic markers
Subjects
Details
- ISSN :
- 2162402X
- Volume :
- 4
- Database :
- OpenAIRE
- Journal :
- OncoImmunology
- Accession number :
- edsair.doi.dedup.....fc454ec1bdcb241d6fd034b8f87a8a87