Open AccessCurcumin improves the therapeutic efficacy of L isteria at ‐ M age‐b vaccine in correlation with improved T ‐cell responses in blood of a triple‐negative breast cancer model 4T1
Author(s) -
Singh Manisha,
Ramos Ilyssa,
AsafuAdjei Denise,
QuispeTintaya Wilber,
Chandra Dinesh,
Jahangir Arthee,
Zang Xingxing,
Aggarwal Bharat B.,
Gravekamp Claudia
Publication year - 2013
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.94
Subject(s) - curcumin , immune system , immunology , medicine , vaccination , immunization , immunotherapy , listeria , cancer research , listeria monocytogenes , cancer , biology , pharmacology , bacteria , genetics
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 L isteria monocytogenes ( L isteria at ), encoding tumor‐associated antigens ( TAA ) Mage‐b in a TNBC model 4T1. Two therapeutic vaccination strategies with L isteria at ‐ M age‐b and curcumin were tested. The first immunization strategy involved all L isteria at ‐ M age‐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 L isteria at ‐ M age‐b after tumor development. Here, we demonstrate that curcumin significantly improves therapeutic efficacy of L isteria at ‐ M age‐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 CD 4 and CD 8 T‐cell responses in blood. Our study suggests that curcumin improves the efficacy of L isteria at ‐ M age‐b vaccine against metastases in TNBC model 4T1 through reversal of tumor‐induced immune suppression.