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.

Keywords: biomarkers; cancer; cytokines; diagnosis; inflammation; point of care; prognosis; tumor microenvironment.

Figure 1

Cytokine actions within the tumor microenvironment. Cancer cells, stromal cells and immune cells populate the tumor microenvironment and secrete cytokines to facilitate the events supporting tumor growth. These include tumor cell initiation and proliferation, immunosuppression, angiogenesis, metastasis, and resistance to anti-cancer drugs.

Figure 2

Cytokines for cancer diagnosis and prognosis. Multiple cancer-derived proteins have been established and used at clinics as biomarkers to detect cancer from blood, however other approaches including detection of a set of cytokines, combining cytokines and their soluble receptors, and combining cytokines and cancer proteins may provide better accuracy for cancer diagnosis and prognosis. A highly accurate alternative cancer biomarkers have been proposed which is the cytokine secretion profile of the circulating peripheral immune cells.