CD4 and neoplasm: 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).