Yin and yang of tumor inflammation: How innate immune suppressors shape the tumor microenvironments

Abstract

Pattern recognition-mediated sensing systems direct host immunity towards either antitumor immunosurveillance or protumorigenic inflammation. These activities imply dual and conflicting roles in the regulation of tumor-associated inflammation. On the one hand, recent evidence has revealed that several signaling components and cell-surface receptors suppress innate immune signals and constitute a negative feedback machinery preventing excess and continuous inflammation within tumor microenvironments. On the other hand, these same components also negatively regulate intrinsic tumorigenic activities by targeting nuclear factor-kappaB (NF-jB)-mediated antiapoptotic and inflammatory signals. Furthermore, the activation status of innate immune suppressors may reflect the functional plasticity of interactions between tumor cells and innate immune cells and determine whether tumor inflammation supports anti-or pro-tumorigenic responses. Thus, innate immune suppressors may provide valuable information about the immunogenic or tumorigenic status of tumor-associated inflammation thereby serving as potential biomarkers that predict tumor progression. Comprehensive analysis for identifying general and unique features of each innate immune suppressor in the regulation of tumor inflammation should explore the development of new biomarkers for improving future therapeutic strategies.

High IL-1R8 expression in breast tumors promotes tumor growth and contributes to impaired antitumor immunity

“…The activation of Interleukin-1 (IL-1) receptor family members (ILRs) and Toll-like receptors (TLRs) represents a critical early innate immune sensing event promoting immunosurveillance and antitumor immunity [ 5 – 7 ]. ILRs and TLRs activation ignites a signal transduction cascade with pro-inflammatory outcomes, including the activation of NF-κB and the secretion of pro-inflammatory cytokines such as Type I IFNs and TNFα, which are in turn necessary for natural killer (NK) and dendritic cell (DC) activation, together with CD8 + T cell priming against tumor antigens and trafficking into the TME [ 8 – 10 ].…”

Germline variation in inflammation-related pathways and risk of Barrett's oesophagus and oesophageal adenocarcinoma

“…Inflammation may act at multiple stages of disease development to disrupt tissue homeostasis, induce aberrant proliferative responses, modulate the tumor microenvironment, and compromise immune surveillance [12, 13, 14]. Inflammatory physiological changes such as oxidative stress are known to exert downstream genotoxic effects [15], and when sustained over extended periods, can promote the emergence of cancer-initiating mutations.…”

Microbiota and Immune Responses in Colon Cancer

“…This process has 3 phases: elimination, equilibrium, and escape. 41 Experimental evidence supports the idea that inflammation promotes tumor development, 42 but the role of the adaptive immune reaction is still comparatively unclear based on multiple murine and human studies. Although the presence of high density of tumor-infiltrating lymphocytes (TIL) has been mostly associated with a better prognosis in CRC, the prognostic value of the regulatory T cells (Tregs) recruitment has been controversial.…”