title: 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.
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.
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine 1300 Morris Park Avenue, Bronx, New York, 10461.
authors.forename: Manisha
authors.initials: M
authors.lastname: Singh
authors.forename: Ilyssa
authors.initials: I
authors.lastname: Ramos
authors.forename: Denise
authors.initials: D
authors.lastname: Asafu-Adjei
authors.forename: Wilber
authors.initials: W
authors.lastname: Quispe-Tintaya
authors.forename: Dinesh
authors.initials: D
authors.lastname: Chandra
authors.forename: Arthee
authors.initials: A
authors.lastname: Jahangir
authors.forename: Xingxing
authors.initials: X
authors.lastname: Zang
authors.forename: Bharat B
authors.initials: BB
authors.lastname: Aggarwal
authors.forename: Claudia
authors.initials: C
authors.lastname: Gravekamp
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000276:immunology*; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003474:Curcumin / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D005260:Female; D007114:Immunization; D018664:Interleukin-12 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D008089:Listeria monocytogenes / Q000276:immunology*; D008325:Mammary Neoplasms, Experimental; D051379:Mice; D022423:Myeloid Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D009362:Neoplasm Metastasis; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D064726:Triple Negative Breast Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy*
chemical_list: D000970:Antineoplastic Agents; D001428:Bacterial Vaccines; D019496:Cancer Vaccines; D015850:Interleukin-6; D018664:Interleukin-12; D003474:Curcumin
keywords: Cancer vaccines; T cells; curcumin; metastases; triple-negative breast cancer