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

Elinav, Eran; Nowarski, Roni; Thaiss, Christoph A.; Hu, Bo; Jin, Chengcheng; Flavell, Richard A.

doi:10.1038/nrc3611

Cited by 1,657 publications

(1,343 citation statements)

References 151 publications

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“…Inflammation plays an essential role in initiating tumorigenesis by damaging specific tissues 100 (Figure 3). In these models, neutrophils are attracted to tumor-prone tissues via the CXCR2 ligands, CXCL1, CXCL2 and CXCL5 [101][102][103][104] .…”

Section: Neutrophils and Tumor Initiationmentioning

confidence: 99%

Neutrophils in cancer: neutral no more

2016

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SummaryNeutrophils are indispensable antagonists of microbial infection and facilitators of wound healing. In the cancer setting, a newfound appreciation for neutrophils has come into view.The traditionally held belief that neutrophils are inert bystanders is being challenged by recent literature. Emerging evidence indicates that tumors manipulate neutrophils, sometimes early in their differentiation process, to create diverse phenotypic and functional polarization states able to alter tumor behavior. In this Review, we discuss the involvement of neutrophils in cancer initiation and progression, and their potential as clinical biomarkers and therapeutic targets. 2The name neutrophil -given to polymorphonuclear, granulocytic cells by Paul Ehrlich in the late 19th century -is based on the inability of these cells to retain acidic or basic dyes and for their preferential uptake of pH neutral dyes 1 . Although their neutral staining led to the identification of these cells, neutrophils in the cancer setting are anything but neutral.Neutrophils in tumor-bearing hosts can oppose or potentiate cancer progression. These two types of behavior are controlled by signals emanating from cancer cells or stromal cells within the tumor microenvironment, which educate neutrophils to execute the demise of the tumor or facilitate support networks that lead to its expansive spread. These functions can occur locally in or around the tumor microenvironment, as well as systemically in distant organs.Until the past few years, other immune cells such as macrophages have overshadowed the role of neutrophils in cancer. But recent studies and the development of new genetic tools have provided the cancer community with new insights into the profound influence of these dynamic cells by uncovering distinct capabilities for neutrophils throughout each step of carcinogenesis: from tumor initiation to primary tumor growth to metastasis.During these processes, neutrophils take on different phenotypes and sometimes opposing functions. Emerging evidence also indicates that these cells are highly influential, and are able to change the behavior of other tumor-associated cell types -primarily other immune cells. In this Review, we focus on how tumors manipulate the generation and release of neutrophils from the bone marrow. We discuss the mechanisms identified in animal models by which neutrophils participate in tumor initiation, growth and metastasis. Finally, we highlight the potential of these cells as clinical biomarkers and therapeutic targets. In humans, neutrophils are the most abundant immune cell population, representing 50-70% of all leukocytes. Over 10 11 neutrophils may be produced per day 2 , and tumors can increase this number by even more. Indeed, patients with various cancer types, including but not limited to breast, lung and colorectal cancer, often exhibit increased numbers of circulating neutrophils 3,4 . Recent studies have identified key pathways that tumors exploit to disrupt normal neutrophil homeostasis and these are discuss...

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Section: Neutrophils and Tumor Initiationmentioning

confidence: 99%

Neutrophils in cancer: neutral no more

2016

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“…Recently, the gut microbiome has been shown to play a crucial role in health, as well as in diseases such as obesity,16 inflammatory bowel disease,17, 18 diabetes,19, 20 non‐alcoholic fatty liver disease,21, 22, 23 and several types of cancers 24, 25. Experimental evidence indicates that the human intestinal microbiome can influence tumor development and progression in the gastrointestinal tract by damaging DNA, activating oncogenic signaling pathways, producing tumor‐promoting metabolites, and suppressing the antitumor immune response 7, 25, 26, 27, 28, 29. As the gastrointestinal microbiota can be modified through the rational deployment of antibiotics, probiotics, and prebiotics,30, 31, 32 a better understanding of the relationship between human cancer and the microbiome may have clinical implications.…”

Section: Introductionmentioning

confidence: 99%

Review of the gut microbiome and esophageal cancer: Pathogenesis and potential clinical implications

Baba

Iwatsuki

Yoshida

et al. 2017

Annals of Gastroent Surgery

104

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Esophageal cancer ranks among the most aggressive malignant diseases. The limited improvements in treatment outcomes provided by conventional therapies have prompted us to seek innovative strategies for treating this cancer. More than 100 trillion microorganisms inhabit the human intestinal tract and play a crucial role in health and disease conditions, including cancer. The human intestinal microbiome is thought to influence tumor development and progression in the gastrointestinal tract by various mechanisms. For example, Fusobacterium nucleatum, which primarily inhabits the oral cavity and causes periodontal disease, might contribute to aggressive tumor behavior through activation of chemokines such as CCL20 in esophageal cancer tissue. Composition of the intestinal microbiota is influenced by diet, lifestyle, antibiotics, and pro‐ and prebiotics. Therefore, by better understanding how the bacterial microbiota contributes to esophageal carcinogenesis, we might develop novel cancer prevention and treatment strategies through targeting the gastrointestinal microflora. This review discusses the current knowledge, available data and information on the relationship of microbiota with esophagitis, Barrett's esophagus, esophageal adenocarcinoma and squamous cell carcinoma.

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“…Butyrate and acetate, which are fermentation products from dietary fibers metabolized by gut microbiota exert antiinflammatory activity and regulate the infiltration of macrophages 143 . Thus, alterations in the microbiome induce pro-inflammatory responses that may contribute to tumor initiation and development 144 . Moreover, gut microbiota is a major donor of acetyl groups in histone acetylation reactions, which is an epigenetic regulatory mechanism influencing gene expression at the chromatin level 145 .…”

Section: Stress As a Modulator Of Immune Response In Depression And Cmentioning

confidence: 99%

Depression in cancer: The many biobehavioral pathways driving tumor progression

Bortolato

Hyphantis

Valpione

et al. 2017

Cancer Treatment Reviews

261

179

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Major Depressive Disorder (MDD) is common among cancer patients, with prevalence rates up to four-times higher than the general population. Depression confers worse outcomes, including non-adherence to treatment and increased mortality in the oncology setting. Advances in the understanding of neurobiological underpinnings of depression have revealed shared biobehavioral mechanisms may contribute to cancer progression. Moreover, psychosocial stressors in cancer promote:(1) inflammation and oxidative/nitrosative stress; (2) a decreased immunosurveillance; and (3) a dysfunctional activation of the autonomic nervous system and of the hypothalamic-pituitary-adrenal axis. Consequently, the prompt recognition of depression among patients with cancer who may benefit of treatment strategies targeting depressive symptoms, cognitive dysfunction, fatigue and sleep disturbances, is a public health priority. Moreover, behavioral strategies aiming at reducing psychological distress and depressive symptoms, including addressing unhealthy diet and life-style choices, as well as physical inactivity and sleep dysfunction, may represent important strategies not only to treat depression, but also to improve wider cancer-related outcomes. Herein, we provide a comprehensive review of the intertwined biobehavioural pathways linking depression to cancer progression. In addition, the clinical implications of these findings are critically reviewed.

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

Cited by 1,657 publications

References 151 publications

Neutrophils in cancer: neutral no more

Neutrophils in cancer: neutral no more

Review of the gut microbiome and esophageal cancer: Pathogenesis and potential clinical implications

Depression in cancer: The many biobehavioral pathways driving tumor progression

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