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.