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Inflammation-induced cancer: crosstalk between tumours, immune cells and microorganisms

Key Points

  • Inflammation is causally related to cancer development, through processes that involve genotoxicity, aberrant tissue repair, proliferative responses, invasion and metastasis.

  • Major inflammatory pathways that are involved in inflammation-induced carcinogenesis converge at the level of the transcription factors signal transducer and activator of transcription 3 (STAT3) and nuclear factor-κB (NF-κB).

  • Tumours modulate the inflammatory environment by the secretion of soluble growth factors and chemoattractants, which render inflammatory cells suppressive against anticancer T cell responses.

  • In around 20% of all cases, microbial organisms are the causative agents of cancer-inducing inflammation.

  • In addition to bona fide pathogens, pathobionts of the commensal microbiota have recently been recognized as being involved in inflammatory processes that promote tumour growth.

  • A better understanding of the role of the microbiota in inflammation-induced cancer might prospectively lead to targeted antimicrobial therapies against cancer initiation or progression.

Abstract

Inflammation is a fundamental innate immune response to perturbed tissue homeostasis. Chronic inflammatory processes affect all stages of tumour development as well as therapy. In this Review, we outline the principal cellular and molecular pathways that coordinate the tumour-promoting and tumour-antagonizing effects of inflammation and we discuss the crosstalk between cancer development and inflammatory processes. In addition, we discuss the recently suggested role of commensal microorganisms in inflammation-induced cancer and we propose that understanding this microbial influence will be crucial for targeted therapy in modern cancer treatment.

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Figure 1: Influence of inflammatory signalling on carcinogenesis.
Figure 2: Influence of cancer cells on inflammatory signalling.
Figure 3: Commensals and pathobionts as inducers of cancer development.
Figure 4: The multifaceted role of inflammasomes in cancer development.

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Acknowledgements

The authors thank all members of the Elinav and Flavell laboratories for scientific suggestions and discussion. This work was supported by the Marie Curie Integration and Helmsley Charitable Foundation grants (to E.E.), by the Howard Hughes Medical Institute and a grant from the US Department of Defense 11-1-0745 (to R.A.F.) and a United States–Israel Binational Foundation grant (to E.E. and R.A.F.). C.A.T. receives a Boehinger Ingelheim Fonds Ph.D. Fellowship. R.N. is supported by a fellowship from the Jane Coffin Childs Memorial Fund, and C.J. was a recipient of a Trudeau Fellowship from Yale University, USA.

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Correspondence to Eran Elinav or Richard A. Flavell.

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Glossary

Tumour microenvironment

Cellular and non-cellular components of the tissue that surrounds and influences tumour growth. Crucial components of the tumour microenvironment are immune cells, blood vessels, fibroblasts, extracellular matrix and other stromal cells.

Inflammasome

An intracellular multiprotein complex of the innate immune system, consisting of sensor proteins of the NOD-like receptor (NLR) family, adaptor proteins and the pro-inflammatory serine protease caspase 1. The function of the inflammasome is to cleave the cytokines pro-interleukin-1β and pro-interleukin-18 into their biologically active forms.

Senescence-associated secretory phenotype

(SASP). A common profile of secreted factors, induced during cellular senescence. These factors include pro-inflammatory cytokines, such as interleukin-1 and interleukin-6, and chemoattractants, such as CXC-chemokine ligand 8.

Genotoxic island

A genomic island in bacteria that encodes proteins with potentially genotoxic — that is, genome-damaging — properties.

Probiotic

Pertaining to microbial species that are introduced into the intestinal microbial ecosystem to exert beneficial effects on the host.

Prebiotics

Interventions (not live microorganisms) that function to stabilize a particular microbial community with a beneficial effect.

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Elinav, E., Nowarski, R., Thaiss, C. et al. Inflammation-induced cancer: crosstalk between tumours, immune cells and microorganisms. Nat Rev Cancer 13, 759–771 (2013). https://doi.org/10.1038/nrc3611

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