A cytokine-mediated link between innate immunity, inflammation, and cancer
Wan-Wan Lin, Michael Karin
Wan-Wan Lin, Michael Karin
Published May 1, 2007
Citation Information: J Clin Invest. 2007;117(5):1175-1183. https://doi.org/10.1172/JCI31537.
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A cytokine-mediated link between innate immunity, inflammation, and cancer

Abstract

It has been established that cancer can be promoted and/or exacerbated by inflammation and infections. Indeed, chronic inflammation orchestrates a tumor-supporting microenvironment that is an indispensable participant in the neoplastic process. The mechanisms that link infection, innate immunity, inflammation, and cancer are being unraveled at a fast pace. Important components in this linkage are the cytokines produced by activated innate immune cells that stimulate tumor growth and progression. In addition, soluble mediators produced by cancer cells recruit and activate inflammatory cells, which further stimulate tumor progression. However, inflammatory cells also produce cytokines that can limit tumor growth. Here we provide an overview of the current understanding of the role of inflammation-induced cytokines in tumor initiation, promotion, and progression.

Authors

Wan-Wan Lin, Michael Karin

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Figure 1

The diagram shows two outcomes of interactions between tumor cells and infiltrating inflammatory and/or immune cells in the tumor microenvironment.

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The diagram shows two outcomes of interactions between tumor cells and i...
Cytokines secreted by tumor and inflammatory/immune cells can either promote tumor development and tumor cell survival or exert antitumor effects. Chronic inflammation develops through the action of various inflammatory mediators, including TNF-α, IL-6, and IL-17, leading to eradication of antitumor immunity and accelerated tumor progression. However, TRAIL, through direct induction of tumor cell apoptosis, IL-10, through antiinflammatory effects, and IL-12, through activation of CTLs and NK cells and expression of cytotoxic mediators, can lead to tumor suppression. The multiple actions of TGF-β (cytotoxic in colon cancer cells, and having both positive and negative effects on the tumor microenvironment) and IL-23 (see Figure 3) explain their dual roles in tumor development.