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Low Dose Decitabine Treatment Induces CD80 Expression in Cancer Cells and Stimulates Tumor Specific Cytotoxic T Lymphocyte Responses
- Source :
- PLoS ONE, Vol 8, Iss 5, p e62924 (2013), PLoS ONE
- Publication Year :
- 2013
- Publisher :
- Public Library of Science (PLoS), 2013.
-
Abstract
- Lack of immunogenicity of cancer cells has been considered a major reason for their failure in induction of a tumor specific T cell response. In this paper, we present evidence that decitabine (DAC), a DNA methylation inhibitor that is currently used for the treatment of myelodysplastic syndrome (MDS), acute myeloid leukemia (AML) and other malignant neoplasms, is capable of eliciting an anti-tumor cytotoxic T lymphocyte (CTL) response in mouse EL4 tumor model. C57BL/6 mice with established EL4 tumors were treated with DAC (1.0 mg/kg body weight) once daily for 5 days. We found that DAC treatment resulted in infiltration of IFN-γ producing T lymphocytes into tumors and caused tumor rejection. Depletion of CD8(+), but not CD4(+) T cells resumed tumor growth. DAC-induced CTL response appeared to be elicited by the induction of CD80 expression on tumor cells. Epigenetic evidence suggests that DAC induces CD80 expression in EL4 cells via demethylation of CpG dinucleotide sites in the promoter of CD80 gene. In addition, we also showed that a transient, low-dose DAC treatment can induce CD80 gene expression in a variety of human cancer cells. This study provides the first evidence that epigenetic modulation can induce the expression of a major T cell co-stimulatory molecule on cancer cells, which can overcome immune tolerance, and induce an efficient anti-tumor CTL response. The results have important implications in designing DAC-based cancer immunotherapy.
- Subjects :
- T-Lymphocytes
medicine.medical_treatment
Cancer Treatment
lcsh:Medicine
Hematologic Cancers and Related Disorders
Mice
Cancer immunotherapy
Basic Cancer Research
Cytotoxic T cell
Promoter Regions, Genetic
lcsh:Science
Immune Response
Oligonucleotide Array Sequence Analysis
Multidisciplinary
Reverse Transcriptase Polymerase Chain Reaction
T Cells
U937 Cells
Hematology
Flow Cytometry
Tumor Burden
Gene Expression Regulation, Neoplastic
medicine.anatomical_structure
Oncology
Azacitidine
B7-1 Antigen
Medicine
Epigenetics
Lymphomas
DNA modification
Research Article
medicine.drug
Acute Myeloid Leukemia
Interleukin 2
Antimetabolites, Antineoplastic
Immune Cells
T cell
Immunology
Decitabine
chemical and pharmacologic phenomena
Biology
Epigenetic Therapy
Immunomodulation
Interferon-gamma
Cell Line, Tumor
Leukemias
Genetics
medicine
Animals
Humans
Cell Proliferation
Immune Evasion
Dose-Response Relationship, Drug
lcsh:R
Neoplasms, Experimental
DNA Methylation
Chemotherapy and Drug Treatment
Molecular biology
Mice, Inbred C57BL
Cancer cell
Interleukin-2
Clinical Immunology
lcsh:Q
Gene expression
K562 Cells
CD8
CD80
T-Lymphocytes, Cytotoxic
Subjects
Details
- ISSN :
- 19326203
- Volume :
- 8
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....eec69541178d49ff43a805d2ecfe0fb1