In this process, macrophages and DCs secrete pro‐inflammatory IL‐1β and TNF‐α under the stimulation of LPS‐induced TLR4 signaling and tumor cell debris.[25b] Flagellin has been found to be capable of activating NK cells to produce IFN‐γ through a TLR‐independent pathway involving IL‐18 and Myeloid differentiation factor 88 (MyD88), and the produced IFN‐γ will lower the frequency of CD4+ CD25+ regulatory T cells (Tregs) in the TME.[16, 35] Studies have shown that Salmonella infection can lead to the up‐regulation of connexin 43 (Cx43) in human and murine melanoma cells (Figure 3). This evidence concerns the gene IL18 and neoplasm.