Tumor-Induced Inflammatory Cytokines and the Emerging Diagnostic Devices for Cancer Detection and Prognosis

Abstract

Chronic inflammation generated by the tumor microenvironment is known to drive cancer initiation, proliferation, progression, metastasis, and therapeutic resistance. The tumor microenvironment promotes the secretion of diverse cytokines, in different types and stages of cancers. These cytokines may inhibit tumor development but alternatively may contribute to chronic inflammation that supports tumor growth in both autocrine and paracrine manners and have been linked to poor cancer outcomes. Such distinct sets of cytokines from the tumor microenvironment can be detected in the circulation and are thus potentially useful as biomarkers to detect cancers, predict disease outcomes and manage therapeutic choices. Indeed, analyses of circulating cytokines in combination with cancer-specific biomarkers have been proposed to simplify and improve cancer detection and prognosis, especially from minimally-invasive liquid biopsies, such as blood. Additionally, the cytokine signaling signatures of the peripheral immune cells, even from patients with localized tumors, are recently found altered in cancer, and may also prove applicable as cancer biomarkers. Here we review cytokines induced by the tumor microenvironment, their roles in various stages of cancer development, and their potential use in diagnostics and prognostics. We further discuss the established and emerging diagnostic approaches that can be used to detect cancers from liquid biopsies, and additionally the technological advancement required for their use in clinical settings.

Circulating Cytokines in Metastatic Breast Cancer Patients Select Different Prognostic Groups and Patients Who Might Benefit from Treatment beyond Progression

“…However, many other Th-2 cytokines were higher in C3 T1 than in C2 T1 . This observation stresses the concept that focusing on a single cytokine is not adequate, as cytokines interact with each other as previously reported [1].…”

“…The tumor microenvironment (TME) drives the dynamic interaction between tumor and immune cells, largely mediated by cytokines and chemokines that exert their biological actions even distantly moving through blood circulation, for instance supporting immunecell recruitment and cancer metastatization [1].…”

Elevated Interleukin-6 Levels in the Circulation and Peritoneal Fluid of Patients with Ovarian Cancer as a Potential Diagnostic Biomarker: A Systematic Review and Meta-Analysis

“…Within the tumor microenvironment, the OC cells and other stromal cells secrete proinflammatory cytokines, such as IL6 and others. Several studies have further shown that increased inflammation levels in the tumor microenvironment promote poorer prognosis for OC (reviewed in [22,29]). Here, we analyzed published articles in Medline and Embase databases that measured IL6 in the circulation and the peritoneal fluid of women with OC in order to provide fundamental baselines on the absolute concentration levels of IL6 in various stages of this disease, as well as to determine the potential of IL6 as a biomarker for not only the late-stage, but also for the detection of the early-stage OC, which is currently difficult to diagnose.…”

“…Ascitic IL6 thus has the potential to be used as a minimally-invasive diagnostic biomarker for OC. Biomarkers with high sensitivity and specificity that facilitate early detection will improve quality of life by increasing progression-free and overall survival of OC patients [27,29].…”

Inflammation, Fibrosis and Cancer: Mechanisms, Therapeutic Options and Challenges

“…While they attract immune cells in the microenvironment (chemokines) or lead to the proliferation of immune cells, cytokines can also enhance oncogenic transformation, promote metabolic changes and hypoxia, thus favoring tumorigenesis. The cytokine-induced inflammatory response whose initial goal is to resolve the underlying insult can promote tumorigenesis as various molecular pathways are common to inflammation and carcinogenesis response pathways [82]. Following tumorigenesis, malignant cells can also secrete tumor-promoting cytokines, exerting their actions through autocrine mechanisms.…”