Myeloid-derived suppressor cells (MDSCs) are one of the major components of the tumor microenvironment (TME), and are the main mediators of tumor-induced immunosuppression. Recent studies have reported that the survival, differentiation and immunosuppressive activity of MDSCs are affected by the Toll-like receptor (TLR) signaling pathway. However, the regulatory effect of TLR signaling on MDSCs remains controversial. TLR-induced MDSC can acquire different immunosuppressive activities to influence the immune response that can be either beneficial or detrimental to cancer immunotherapy. The present review summarizes the effects of TLR signals on the number, phenotype and inhibitory activity of MDSCs, and their role in cancer immunotherapy, which cannot be ignored if effective cancer immunotherapies are to be developed for the immunosuppression of the TME.

Tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6), an E3 ubiquitin ligase, is a signal transduction molecule shared by the interleukin-1 receptor (IL-1R)/Toll-like receptor (TLR) family and the TNFR superfamily. TRAF6 has a unique TRAF domain and RING finger domain that mediate intracellular signaling events. In the immune system, TRAF6-mediated signaling has been shown to be critical for the development, homeostasis, and activation of a variety of immune cells, including B cells, T cells, dendritic cells, and macrophages. Although the pathogenesis and etiology of autoimmune diseases and cancer are not fully understood, it is worth noting that existing studies have shown that TRAF6 is involved in the pathogenesis and development of a variety of these diseases. Herein, we reviewed the role of TRAF6 in certain immune cells, as well as the function and potential effect of TRAF6 in autoimmune diseases and cancer. Our review indicates that TRAF6 may be a novel target for autoimmune diseases and cancer.

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We explored the effect of a recombinant mucin1-maltose-binding protein vaccine, including immunization cycles of recombinant mucin1-maltose-binding protein (MUC1-MBP) and CpG 2006 on T cell responses to human MUC1-overexpressing mouse melanoma B16 cells (B16-MUC1) melanoma in mice. We found that the vaccine had a significant antitumor effect, with the most obvious tumor-suppressive effect being observed in mice immunized five times. After more than five immunizations, the tumor inhibition rate decreased from 81.67% (five immunizations) to 43.67% (eight immunizations). To study the possible mechanism, Mucin-1(MUC1)-specific antibodies, IFN-γ secretion by lymphocytes, and cytotoxic T lymphocyte (CTL) cytotoxicity were measured by enzyme-linked immunosorbent assay (ELISA) and a real-time cell analyzer (RTCA). T cell subsets and immunosuppressive cells in the mouse spleen and tumor microenvironment were analyzed by FACS. These results showed that five immunizations activated MUC1-specific Th1 and CTL and reduced the ratio of myeloid-derived suppressor cells (MDSCs) and Th17 in mice more significantly than eight immunizations, indicating that excessive frequency of the immune cycle leads to the increased numbers of immunosuppressive cells and decreased numbers of immunostimulatory cells, thereby inhibiting antitumor immune activity. This data provide an experimental foundation for the clinical application of a recombinant MUC1-MBP vaccine.