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.
Highlights
TUMOR MICROENVIRONMENT, INFLAMMATION, AND CYTOKINESThe initiation and subsequent development of a tumor into a metastatic state are driven by genetic or epigenetic changes and greatly determined by the action of the tumor microenvironment (TME) [1]
The dynamic interactions between tumor cells and the non-transformed cells are key in determining the progression of cancer, as these could either suppress or promote cancer initiation, growth, migration, and metastasis, as well as cancer recurrence and drug resistance [2], such as stromal cell cues that help cancer growth and invasion, and endothelial cell responses that promote the generation of new blood vessels to the cancer site
In the TME, certain immune cell infiltrates are correlated with improved cancer outcomes, some studies show that unresolved host immune reactivity could lead to chronic inflammation and promotes tumor growth
Summary
TUMOR MICROENVIRONMENT, INFLAMMATION, AND CYTOKINESThe initiation and subsequent development of a tumor into a metastatic state are driven by genetic or epigenetic changes and greatly determined by the action of the tumor microenvironment (TME) [1]. Combining measurements of cancer-specific proteins with the circulating cytokines from liquid biopsies such as blood, could help accurately detect cancer, and may further determine its stage. We will discuss the current and emerging technologies (Table 1) that could be used to detect circulating cytokines and secreted signatures of cytokines from peripheral cells, with multiplexing capacity that provide a high level of specificity, and sensitivity to support cancer diagnosis and prognosis.
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