Cancer-Related Inflammation

Abstract

Solid tumors consist of neoplastic cells, non-malignant stromal cells, and migratory hematopoietic cells. Complex interactions between the cell types in this microenvironment regulate tumor growth, progression, metastasis, and angiogenesis. The cells and mediators of inflammation form a major part of the epithelial tumor microenvironment. In some cancers, inflammatory conditions precede development of malignancy; in others, oncogenic change drives a tumor-promoting inflammatory milieu. Whatever its origin, this "smoldering" inflammation aids proliferation and survival of malignant cells, stimulates angiogenesis and metastasis, subverts adaptive immunity, and alters response to hormones and chemotherapy. Cytokines are major mediators of communication between cells in the inflammatory tumor microenvironment. It is known that neoplastic cells often over-express proinflammatory mediators including proteases, eicosanoids, cytokines, and chemokines. Several cytokines such as macrophage migratory inhibitory factor (MIF), TNF-α, IL-6, IL-17, IL-12, IL-23, IL-10, and TGF-β have been linked with both experimental and human cancers and can either promote or inhibit tumor development. MIF is a major cytokine in many cancers and there is evidence that the cytokine is produced by both malignant cells and infiltrating leukocytes. In this article we will discuss the role of cancer-associated inflammation and the particular role of MIF in malignant disease.

Loss of autophagy enhances MIF/macrophage migration inhibitory factor release by macrophages

“…Moreover, MIF is implicated in the pathology of autoimmune diseases, including rheumatoid arthritis, systemic lupus erythematosus and atherosclerosis 12,13,39 and is linked with cancer-associated inflammation, promoting tumor growth in a number of different cancers. 40 Clinically, the role for MIF in reducing glucocorticoid sensitivity is particularly important, given the wide use of these drugs in the treatment of inflammatory diseases. Moreover, a growing body of evidence has highlighted significant links between autophagy and the regulation of inflammation and autoimmune disease.…”

Laparoscopic surgery for colorectal cancer is not associated with an increase in the circulating levels of several inflammation-related factors

“…It is of interest that most of the circulating factors found to be increased in CRC patients are considered pro-inflammatory mediators thus suggesting that cancer patients display an inflammatory state which is due to and sustained by tumor bulk and likely involving both neoplastic as well as nonmalignant stromal and inflammatory cells. [5][6][7][8]15,22 Several potent soluble mediators are released during inflammation and they are finely regulated in a temporally and spatially regulated fashion to prevent them from acting outside the process itself. If this occurs, the same factors playing important roles during the inflammation process can promote unintended results, including tumor development 3,4 and the findings of the present study confirm that in cancer patients they are mainly produced within tumor microenvironment.…”

“…5,[9][10][11][21][22][23][24][25] To our knowledge, our study if the first using a xMAP system to simultaneously assess expression levels of several circulating factors in cancer patients at the baseline and in the post-operatory while carefully controlling for cigarette smoking and other potential confounders.…”

“…2,3 Although the precise mechanisms linking chronic inflammation to cancer development are unknown, several factors have been implicated in this association including the activation of tissue repair and regeneration processes. [3][4][5] In this scenario, cancers have been also described as "wounds that won't heal" 6 and several important phenomena occurring during the process of tumor development (i.e., the so-called epithelial mesenchymal transition or EMT) appear to be, at least in part, mediated by cytokines and several other soluble inflammatory molecules and growth factors. Most of these soluble mediators are physiologically released in the sites of wound repair but are also present in tumor microenvironment being able to promote a modification of epithelial cells phenotype.…”

“…Activation of NF-kB, the major pathway that regulates immune inflammatory responses, is a frequent event in cancer cells (tumorigenesis) and can induce pro-inflammatory cytokines, such as TNF-a, IL-1b, and IL-6. 5 In this study we took advantage of a Multi-Analyte Profiling technology to perform a case-control study comparing the levels of several circulating cytokines, chemokines and growth factors in colorectal cancer patients compared to non-neoplastic patients and to evaluate the same parameters during a time course following laparoscopic surgery for colorectal cancer.…”