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The review that made the immune cells inside a tumour part of the disease: long-running inflammation, whether from infection, irritation or the tumour's own signals, supplies growth factors, blood vessels and DNA damage that help cancers start and spread.
Coussens and Werb drew together epidemiology and mouse genetics to argue that chronic inflammation is a cause of cancer rather than a bystander. They reviewed the infections and inflammatory conditions tied to specific cancers, such as Helicobacter pylori and stomach cancer, hepatitis viruses and liver cancer, and inflammatory bowel disease and bowel cancer, and described how macrophages, neutrophils and mast cells in the tumour microenvironment release cytokines, proteases, reactive oxygen species and angiogenic factors that promote proliferation, invasion and new blood vessels. They cited estimates that about 15% of cancers worldwide are linked to infection and proposed that anti-inflammatory strategies could prevent or treat cancer.
This paper is why the tumour microenvironment is studied as intensely as the cancer cell itself. It underpins vaccination against HPV and hepatitis B as cancer prevention, aspirin and anti-inflammatory trials in bowel cancer, and the current work on macrophages and myeloid cells as immunotherapy targets.
This review is the standard map of the tumour microenvironment and the reason microenvironment-directed drugs, from anti-angiogenics to macrophage and fibroblast targeting agents, are developed alongside tumour-cell-directed ones.
This paper is the molecular sequel to the 2002 inflammation and cancer review and the basis for IL-6, JAK-STAT and NF-kB directed strategies in cancer as well as for aspirin and other anti-inflammatory prevention trials.
Together with the 2002 Nature review this essay put inflammation on the cancer research agenda; the tumour-associated macrophage and IL-6 work that followed, and the aspirin prevention trials, trace back to it.
Shares Grivennikov, Greten and Karin 2010: immunity, inflammation and cancer, Gastric & gastro-oesophageal junction cancer, Colorectal cancer.
Shares Balkwill and Mantovani 2001: inflammation and cancer, back to Virchow?, Inflammation, Immune system, Microenvironment and inflammation: tumours as wounds that do not heal.
Shares Balkwill and Mantovani 2001: inflammation and cancer, back to Virchow?, Grivennikov, Greten and Karin 2010: immunity, inflammation and cancer, Inflammation, Microenvironment and inflammation: tumours as wounds that do not heal.
Shares Quail and Joyce 2013: microenvironmental regulation of tumour progression and metastasis, Microenvironment and inflammation: tumours as wounds that do not heal.
Shares Grivennikov, Greten and Karin 2010: immunity, inflammation and cancer, Inflammation, Microenvironment and inflammation: tumours as wounds that do not heal.
Shares Inflammation, Immune system.
Shares Balkwill and Mantovani 2001: inflammation and cancer, back to Virchow?, Quail and Joyce 2013: microenvironmental regulation of tumour progression and metastasis.
Shares Grivennikov, Greten and Karin 2010: immunity, inflammation and cancer, Microenvironment and inflammation: tumours as wounds that do not heal.