Neutralizing Tumor-Promoting Chronic Inflammation: A Magic Bullet?

Coussens, Lisa M.; Zitvogel, Laurence; Palucka, A. Karolina

doi:10.1126/science.1232227

Cited by 975 publications

(857 citation statements)

References 73 publications

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“…5,6 It is driven by the accumulation of various immune and inflammatory cells and soluble inflammatory mediators, such as cytokines, chemokines, growth factors, lipid molecules, reactive oxygen (ROS), and nitrogen species. 5 The interaction between these immune and inflammatory cells and mediators leads to generation of autocrine and paracrine signals that foster cancer growth and metastases.…”

Section: Introductionmentioning

confidence: 99%

Human mast cells promote colon cancer growth via bidirectional crosstalk: studies in 2D and 3D coculture models

Blokhuis

Derks

et al. 2018

OncoImmunology

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Chronic inflammation drives the development of colorectal cancer (CRC), where tumor-infiltrating immune cells interact with cancer cells in a dynamic crosstalk. Mast cells (MC), one of earliest recruited immune cells, accumulate in CRC tissues and their density is correlated with cancer progression. However, the exact contribution of MC in CRC and their interaction with colon cancer cells is poorly understood. Here, we investigated the impact of primary human MC and their mediators on colon cancer growth using 2D and 3D coculture models. Primary human MC were generated from peripheral CD34+ stem cells. Transwell chambers were used to analyze MC chemotaxis to colon cancer. Colon cancer cells HT29 and Caco2 differentially recruited MC by releasing CCL15 or SCF, respectively. Using BrdU proliferation assays, we demonstrated that MC can directly support colon cancer proliferation and this effect was mediated by their cellular crosstalk. 3D coculture models with cancer spheroids further confirmed the pro-tumor effect of MC on colon cancer growth, where direct cell-cell contact is dispensable and increased production of multiple soluble mediators was detected. Moreover, TLR2 stimulation of MC promoted stronger growth of colon cancer spheroids. By examining the transcriptome profile of colon cancer-cocultured MC versus control MC, we identified several MC marker genes, which were deregulated in expression. Our study provides an advanced in vitro model to investigate the role of human MC in cancer. Our data support the detrimental role of MC in CRC development and provide a molecular insight into the cellular crosstalk between MC and colon cancer cells.

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Section: Introductionmentioning

confidence: 99%

Human mast cells promote colon cancer growth via bidirectional crosstalk: studies in 2D and 3D coculture models

Blokhuis

Derks

et al. 2018

OncoImmunology

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“…Inflammatory cytokines and chronic inflammation correlate with increased tumor incidence and a worsened prognosis for patients with cancer (18). The development and progression of tumors in chronically inflamed tissue is thought to be the consequence of increased compensatory cell proliferation, a tumor-promoting microenvironment with increased angiogenesis and proteolytic activity, an increased mutation rate due to the release of oxygen radicals, and the conspicuous absence of tumor immunosurveillance by cytotoxic T cells.…”

Section: Il-10 Controls Tumor-promoting Inflammationmentioning

confidence: 99%

IL-10: Master Switch from Tumor-Promoting Inflammation to Antitumor Immunity

Oft

2014

Cancer Immunology Research

243

184

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Human cancer is characterized by deficits in antigen-specific immunity and intratumoral CD8 þ T cells. On the other hand, inflammatory macrophages and mediators of chronic inflammation are highly prevalent in patients with late-stage cancer. Intratumoral T-cell deficiency and chronic inflammation have been linked independently to a poor prognosis in patients with cancer, and therapeutic approaches to overcome either pathology separately are in clinical testing. The anti-inflammatory cytokine interleukin (IL)-10 suppresses macrophage and proinflammatory Th17 T-cell responses by inhibiting the inflammatory cytokines IL-6 and IL-12/23. Corroborating the anti-inflammatory action of IL-10, deficiency in IL-10 leads to a stimulation of inflammatory responses and inflammatory bowel disease. The anti-inflammatory role of IL-10 fostered the assumption that IL-10 undermines the immune response to cancer. However, mice and humans deficient in IL-10 signaling develop tumors spontaneously and at high rates. Overexpression of IL-10 in models of human cancer or treatment with a pegylated IL-10 (PEG-IL-10) led to tumor rejection and long-lasting tumor immunity. IL-10 stimulates cytotoxicity of CD8 þ T cells and the expression of IFN-g in CD8 þ T cells. IL-10-induced tumor rejections are dependent on the expression of IFN-g and granzymes in tumor-resident CD8 þ T cells and the upregulation of MHC molecules. These findings reconcile earlier clinical data, which showed that recombinant IL-10 increased IFN-g and granzymes in the blood of treated individuals. PEG-IL-10 is therefore a unique therapeutic agent, which simultaneously stimulates antitumor immunity and inhibits tumor-associated inflammation.

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“…Normal tissue microenvironment can suppress malignancy, while certain pathogenetic tissue features can induce tumor progression. 63,64 TAMs: Tumor-associated macrophages Macrophages are the most represented leukocytes in solid tumors and are highly plastic cells. 65 Under the influence of IFNg, macrophages undergo classical M1 polarization, characterized by an immunostimulatory phenotype.…”

Section: Immune Cells In Tc Microenvironmentmentioning

confidence: 99%

The immune network in thyroid cancer

2016

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The immune system plays critical roles in tumor prevention, but also in its initiation and progression. Tumors are subjected to immunosurveillance, but cancer cells generate an immunosuppressive microenvironment that favors their escape from immune-mediated elimination. During chronic inflammation, immune cells can contribute to the formation and progression of tumors by producing mitogenic, prosurvival, proangiogenic and lymphangiogenic factors. Thyroid cancer is the most frequent type of endocrine neoplasia and is the most rapidly increasing cancer in the US. In this review, we discuss recent findings on how different immune cells and mediators can contribute to thyroid cancer development and progression.

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Neutralizing Tumor-Promoting Chronic Inflammation: A Magic Bullet?

Cited by 975 publications

References 73 publications

Human mast cells promote colon cancer growth via bidirectional crosstalk: studies in 2D and 3D coculture models

Human mast cells promote colon cancer growth via bidirectional crosstalk: studies in 2D and 3D coculture models

IL-10: Master Switch from Tumor-Promoting Inflammation to Antitumor Immunity

The immune network in thyroid cancer

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