Inflammation predisposes to the development of cancer and promotes all stages of tumorigenesis. Cancer cells, as well as surrounding stromal and inflammatory cells, engage in well-orchestrated reciprocal interactions to form an inflammatory tumor microenvironment (TME). Cells within the TME are highly plastic, continuously changing their phenotypic and functional characteristics. Here, we review the origins of inflammation in tumors, and the mechanisms whereby inflammation drives tumor initiation, growth, progression, and metastasis. We discuss how tumor-promoting inflammation closely resembles inflammatory processes typically found during development, immunity, maintenance of tissue homeostasis, or tissue repair and illuminate the distinctions between tissue-protective and pro-tumorigenic inflammation, including spatiotemporal considerations. Around 15%-20% of all cancer cases are preceded by infection, chronic inflammation, or autoimmunity at the same tissue or organ site. In such cases, inflammation that promotes cancer is induced and exists long before tumor formation. The most prominent examples include inflammatory bowel disease (IBD), chronic hepatitis, Helicobacter-induced gastritis, or schistostoma-induced bladder inflammation increasing the risk of colorectal cancer (CRC), liver cancer, stomach cancer, or bladder cancer, respectively. There are also various environmental factors that predispose to and promote cancer acting in whole or in part via induction of chronic inflammation, albeit sometimes of low grade and intensity. In this case, inflammation might precede or accompany tumor development. With regard to the host, these factors might be systemic or site and organ specific. For example, inhalation of fine particles, tobacco smoke, and asbestos would primarily cause lung and airway inflammation and promote lung cancer and mesothelioma. On the other hand, low-grade inflammation induced by obesity, hyperglycemia, and excessive lipid accumulation is generally of systemic nature and, as a result, can promote or increase risk of many different cancers, including liver, pancreatic, colon, breast, and other. Type II diabetes, which has previously been considered as an independent risk factor for cancer, might be viewed as a part of obesity-induced inflammation and obesity-related tissue injury leading to cancer sequela. With the rapid emergence of the obesity epidemic in westernized countries, the exact mechanisms of how obesity and obesity-related inflammation promote tumor progression need to be determined in order to mitigate these life-threatening consequences of prevalent metabolic diseases. The action of systemic inflammation can take place even during the late stages of tumor development, as exemplified by tobacco-smoke, obesity-, and bacterial-product-induced inflammation, which activate neutrophils and their extracellular trap formation function to promote breast cancer metastasis into the lungs, according to Florian R. Greten et al., “Inflammation and Cancer: Triggers, Mechanisms, and Consequences,” Immunity 51, July 16, 2019, 27-41, https://doi.org/10.1016/j.immuni.2019.06.025, JIF 43.474 (top 1.2% journals in Immunology).
Inflammatory responses play pivotal roles in cancer development, including tumor initiation, promotion, progression, and metastasis. Cytokines are now recognized as important mediators linking inflammation and cancer, and are therefore potential therapeutic and preventive targets as well as prognostic factors. The interleukin (IL)-6 family of cytokines, especially IL-6 and IL-11, is highly up-regulated in many cancers and considered as one of the most important cytokine families during tumorigenesis and metastasis, according to Koji Taniguchi et al., “IL-6 and related cytokines as the critical lynchpins between inflammation and cancer,” Seminars in Immunology, Volume 26, Issue 1, February 2014, 54-74, https://doi.org/10.1016/j.smim.2014.01.001, JIF 10.671 (top 15% journals in Immunology / top 16% journals in Immunology in 2014).
Inflammatory conditions in selected organs increase the risk of cancer. An inflammatory component is present also in the microenvironment of tumors that are not epidemiologically related to inflammation. Recent studies have begun to unravel molecular pathways linking inflammation and cancer. In the tumor microenvironment, smoldering inflammation contributes to proliferation and survival of malignant cells, angiogenesis, metastasis, subversion of adaptive immunity, reduced response to hormones and chemotherapeutic agents. Recent data suggest that an additional mechanism involved in cancer-related inflammation (CRI) is induction of genetic instability by inflammatory mediators, leading to accumulation of random genetic alterations in cancer cells, according to Francesco Colotta et al., “Cancer-related inflammation, the seventh hallmark of cancer: links to genetic instability,” Carcinogenesis, Volume 30, Issue 7, July 2009, Pages 1073-1081, https://doi.org/10.1093/carcin/bgp127, JIF 4.741 (top 42% journals in Oncology / top 12% journals in Oncology in 2009).
Inflammatory conditions in selected organs increase the risk of cancer. An inflammatory component is present also in the microenvironment of tumours that are not epidemiologically related to inflammation. Compounds of the inflammatory tumour microenvironment include leukocytes, cytokines, complement components, and are orchestrated by transcription factors, such as NFkB and Stat3. Recent studies have begun to unravel molecular pathways linking inflammation and cancer. An intrinsic (driven by genetic events that cause neoplasia) and an extrinsic (driven by inflammatory conditions which predispose to cancer) pathway link inflammation and cancer. Smouldering inflammation in the tumour microenvironment promotes proliferation and survival of malignant cells, angiogenesis, metastasis, subversion of adaptive immunity, response to hormones and chemotherapeutic agents, according to A. Mantovani, “Molecular Pathways Linking Inflammation and Cancer,” Current Molecular Medicine, Volume 10, Issue 4, 2010, 369-373, https://doi.org/10.2174/156652410791316968, JIF 2.616 (top 78% journals in Medicine, Research & Experimental / top 11% journals in Medicine, Research & Experimental in 2010).
Inflammation is often associated with the development and progression of cancer. The cells responsible for cancer-associated inflammation are genetically stable and thus are not subjected to rapid emergence of drug resistance; therefore, the targeting of inflammation represents an attractive strategy both for cancer prevention and for cancer therapy. Tumor-extrinsic inflammation is caused by many factors, including bacterial and viral infections, autoimmune diseases, obesity, tobacco smoking, asbestos exposure, and excessive alcohol consumption, all of which increase cancer risk and stimulate malignant progression. In contrast, cancer-intrinsic or cancer-elicited inflammation can be triggered by cancer-initiating mutations and can contribute to malignant progression through the recruitment and activation of inflammatory cells. Both extrinsic and intrinsic inflammations can result in immunosuppression, thereby providing a preferred background for tumor development. The current review provides a link between inflammation and cancer development. Nitin Singh et al., “Inflammation and cancer,” Annals of African Medicine, 2019 Jul-Sep;18(3):121-126, https://doi.org/10.4103/aam.aam_56_18, JIF N/A.