Cancer Immunotherapy: Priming the Host Immune Response with Live Attenuated Salmonella enterica

Figure 2

Activation of innate and adaptive immune response in the tumor microenviroment by Salmonella enterica. Once Salmonella colonizes tumor tissue, it induces an antitumor innate and adaptive immune response through several mechanisms: (a) promotes proinflammatory cytokines (IFN-γ and TNF-α), while decreases both anti-inflammatory (TGF-β, IL-4) and angiogenic factors (VEGF) associated with tumor growth progression; (b) interactions between bacterial components (LPS and flagellin) and tumor cell receptors as TLR4 or TLR5, respectively, induce cytokine secretions that promotes the recruitment of neutrophils, macrophages, T lymphocytes, B lymphocytes, and dendritic cells to the tumor microenvironment; (c) Salmonella colonization induces the expression of connexin 43; this molecule plays a major role in the cross-presentation of tumor antigens by DCs to CD8⁺ T-cells; (d) the presence of antitumor CD4⁺ T-cell induce the activation and differentiation of B lymphocytes into plasma cells, producing specific antitumor antibodies.

(a)

(b)

(c)

(d)