In this study, we investigated efficacy of lenalidomide in combination with tumor antigen-loaded dendritic cells (DCs) in murine colon cancer model. MC-38 cell lines were injected subcutaneously to establish colon cancer-bearing mice. After tumor growth, lenalidomide (50 mg/kg/day) was injected intraperitoneally on 3 consecutive days in combination with tumor antigen-loaded DC vaccination on days 8, 12, 16, and 20. The tumor antigen-loaded DCs plus lenalidomide combination treatment exhibited a significant inhibition of tumor growth compared with the other groups. These effects were associated with a reduction in immune suppressor cells, such as myeloid-derived suppressor cells and regulatory T cells, with the induction of immune effector cells, such as natural killer cells, CD4+ T cells and CD8+ T cells in spleen, and with the activation of cytotoxic T lymphocytes and NK cells. This study suggests that a combination of tumor antigen-loaded DC vaccination and lenalidomide synergistically enhanced antitumor immune response in the murine colon cancer model, by inhibiting the generation of immune suppressive cells and recovery of effector cells, and demonstrated superior polarization of Th1/Th2 balance in favor of Th1 immune response. This combination approach with DCs and lenalidomide may provide a new therapeutic option to improve the treatment of colon cancer.

We have previously shown that immunization with tumor antigen-loaded dendritic cells (DCs) and the immunomodulating drug, lenalidomide, synergistically potentiates the enhancing antitumor immunity in a myeloma mouse model. In this study, we investigated the immunogenicity of DCs combined with pomalidomide and dexamethasone in a myeloma mouse model. MOPC-315 cells were injected subcutaneously to establish myeloma-bearing mice. Four test groups were used to mimic clinical protocol: (1) PBS control, (2) DCs, (3) pomalidomide + dexamethasone, and (4) DCs + pomalidomide + dexamethasone. The combination of DCs plus pomalidomide and dexamethasone displayed greater inhibition of tumor growth compared to the other groups. This effect was closely related with reduced numbers of immune suppressor cells including myeloid-derived suppressor cells, M2 macrophages, and regulatory T cells, with the induction of immune effector cells such as CD4+ and CD8+ T cells, memory T cells, natural killer (NK) cells, and M1 macrophages, and with the activation of T lymphocytes and NK cells in the spleen. Moreover, the level of the immunosuppressive factor vascular endothelial growth factor was significantly reduced in the tumor microenvironment. The collective findings in the murine myeloma model suggest that tumor antigen-loaded DCs combined with pomalidomide and dexamethasone synergistically enhance antitumor immunity by skewing the immune-suppressive status toward an immune-supportive status.

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Rosacea is a common chronic inflammatory facial disorder. Reactive oxygen species (ROS) have a key role in the pathogenesis of rosacea. In this study, the antioxidant and anti‐inflammatory effects of bilirubin‐based nanoparticles (BRNPs) are investigated in the LL‐37‐induced rosacea‐like mouse model. Effects of BRNPs on rosacea‐like skin inflammation and ROS level of the skin are determined using histological analysis. The expression of genes encoding rosacea‐associated cytokines and chemokines is assessed and the molecular mechanisms of BRNPs against rosacea are investigated using RNA sequencing (RNAseq) analysis. This study reveals that BRNPs significantly alleviate LL‐37‐induced inflammatory manifestation in the rosacea mouse model and reduce the expression of proinflammatory cytokines (interleukin [IL]‐1β, IL‐6, and tumor necrosis factor [TNF]‐α) and chemokines (C‐X‐C motif chemokine ligand 8 [CXCL8] and CXCL10). Moreover, BRNPs preferentially localize at the inflammatory skin lesion, decrease the level of ROS in the skin, and ameliorate the vascular endothelial growth factor expression and vascular changes in the skin induced by LL‐37. Furthermore, these findings provide a mechanism for the efficacy of BRNPs in this experimental model and support BRNPs as a potential therapeutic option for rosacea and other related inflammatory skin disorders.