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Curcumin improves the therapeutic efficacy of Listeria(at)-Mage-b vaccine in correlation with improved T-cell responses in blood of a triple-negative breast cancer model 4T1.
- Source :
-
Cancer medicine [Cancer Med] 2013 Aug; Vol. 2 (4), pp. 571-82. Date of Electronic Publication: 2013 Jul 02. - Publication Year :
- 2013
-
Abstract
- Success of cancer vaccination is strongly hampered by immune suppression in the tumor microenvironment (TME). Interleukin (IL)-6 is particularly and highly produced by triple-negative breast cancer (TNBC) cells, and has been considered as an important contributor to immune suppression in the TME. Therefore, we hypothesized that IL-6 reduction may improve efficacy of vaccination against TNBC cancer through improved T-cell responses. To prove this hypothesis, we investigated the effect of curcumin, an inhibitor of IL-6 production, on vaccination of a highly attenuated Listeria monocytogenes (Listeria(at)), encoding tumor-associated antigens (TAA) Mage-b in a TNBC model 4T1. Two therapeutic vaccination strategies with Listeria(at)-Mage-b and curcumin were tested. The first immunization strategy involved all Listeria(at)-Mage-b vaccinations and curcumin after tumor development. As curcumin has been consumed all over the world, the second immunization strategy involved curcumin before and all therapeutic vaccinations with Listeria(at)-Mage-b after tumor development. Here, we demonstrate that curcumin significantly improves therapeutic efficacy of Listeria(at)-Mage-b with both immunization strategies particularly against metastases in a TNBC model (4T1). The combination therapy was slightly but significantly more effective against the metastases when curcumin was administered before compared to after tumor development. With curcumin before tumor development in the combination therapy, the production of IL-6 was significantly decreased and IL-12 increased by myeloid-derived suppressor cells (MDSC), in correlation with improved CD4 and CD8 T-cell responses in blood. Our study suggests that curcumin improves the efficacy of Listeria(at)-Mage-b vaccine against metastases in TNBC model 4T1 through reversal of tumor-induced immune suppression.
- Subjects :
- Animals
Antineoplastic Agents administration & dosage
Apoptosis drug effects
Apoptosis immunology
Bacterial Vaccines administration & dosage
Cancer Vaccines administration & dosage
Cancer Vaccines immunology
Cell Line, Tumor
Cell Proliferation drug effects
Curcumin administration & dosage
Disease Models, Animal
Female
Immunization
Interleukin-12 biosynthesis
Interleukin-6 biosynthesis
Mice
Myeloid Cells drug effects
Myeloid Cells immunology
Myeloid Cells metabolism
Neoplasm Metastasis
T-Lymphocyte Subsets metabolism
Triple Negative Breast Neoplasms pathology
Antineoplastic Agents pharmacology
Bacterial Vaccines immunology
Curcumin pharmacology
Listeria monocytogenes immunology
Mammary Neoplasms, Experimental
T-Lymphocyte Subsets immunology
Triple Negative Breast Neoplasms immunology
Triple Negative Breast Neoplasms therapy
Subjects
Details
- Language :
- English
- ISSN :
- 2045-7634
- Volume :
- 2
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Cancer medicine
- Publication Type :
- Academic Journal
- Accession number :
- 24156030
- Full Text :
- https://doi.org/10.1002/cam4.94