Cancer Cell–Autonomous Parainflammation Mimics Immune Cell Infiltration

Abstract

Parainflammation is a unique variant of inflammation, characterized by epithelial-autonomous activation of inflammatory response. Parainflammation has been shown to strongly promote mouse gut tumorigenesis upon p53 loss. In a recent study, we explored the prevalence of parainflammation in human cancer and determined its relationship to certain molecular and clinical parameters affecting treatment and prognosis. Parainflammation can be identified from a 40-gene signature, and is found in both carcinoma cell lines and a variety of primary tumors, independently of tumor microenvironment. Here we discuss the implications of our findings in analyses of tumor microenvironment, suggesting that as tumor cell gene expression may often mimic immune and inflammatory infiltration, caution should be applied when interpreting tumor expression data. We also address the connection between parainflammation and prevalence of p53 mutations in specific types of tumors, and cancer prevention by regular usage of NSAIDs. We suggest that parainflammation may serve as a novel biomarker for screening patients who may particularly benefit from NSAID treatment.

siRNA Library Screening Identifies a Druggable Immune-Signature Driving Esophageal Adenocarcinoma Cell Growth

“…EAC develops in a background of GERD-induced inflammation and it recently was postulated that inflammatory factors may be directly responsible for the induction of metaplasia development rather than a process of caustic erosion followed by metaplastic replacement. 17 Furthermore, a growing body of evidence has defined the epithelial-autonomous activation of inflammatory responses termed parainflammation in mice, 39 , 40 , 62 human beings, 39 and numerous carcinoma cell lines. 39 The data suggest that the low-grade epithelial inflammation induced by a stressor in conjunction with tumor-suppressor loss (p53 mutation) results in a macrophage mimicry by tumor cells.…”

“… 39 The data suggest that the low-grade epithelial inflammation induced by a stressor in conjunction with tumor-suppressor loss (p53 mutation) results in a macrophage mimicry by tumor cells. 40 , 62 In addition, recent sequencing studies have defined glioblastoma subsets with distinct complement response signature derived from CD45-depleted tumors. 63 Our detection of an enriched immune signature underlying the promoters of EAC cell viability as determined by siRNA library screening, thus is supported by considerable evidence.…”

Assessment of para‑inflammation in a wound healing model

“…M2 macrophages have been demonstrated to participate in tissue repair (15). In addition, tissue-resident macrophages act as sentinels during homeostasis, in order to identify and respond to intrinsic and extrinsic stimuli (10). However, the changes in the expression pattern of M2-associated genes in wound healing are unclear.…”

“…Notably, para-infl amma-�8�. Notably, para-inflammation serves a more complex role in tumor development (10), and can repress or promote tumorigenesis, depending on the activity of the tumor protein p53 �11�. However, the association between para-inflammation and wound healing remains unclear.…”

The Severity of Neurological Dysfunction in Preschool Children, Secondary to Damage Generated During the Perinatal Period, is Associated With a Pro-Inflammatory Pattern of Serum Molecules

“…Recent data suggest that tissue dysfunction, and not only acute damage, can act as an inflammatory trigger. Therefore, even when the primary harmful event has long since disappeared, a perpetual cycle of inflammation-dysfunction-inflammation may occur in the form of low-grade chronic inflammation or chronic parainflammation (19,20), with systemic repercussions (21)(22)(23). Furthermore, any abnormal condition that occurs in the structures of the central nervous system can alter not only its functioning, but also that of other structures that also participate in the response to different intrinsic or extrinsic challenges (24).…”