Abstract
Inflammation is a fundamental physiological response orchestrated by innate immune cells to restore tissue homeostasis. Specialized pro-resolving mediators (SPMs) are involved in active resolution of inflammation but when inflammation is incomplete, chronic inflammation creates a favorable environment that fuels carcinogenesis and cancer progression. Conventional cancer therapy also strengthens cancer-related inflammation by inducing massive tumor cell death that activate surrounding immune-infiltrating cells such as tumor-associated macrophages (TAMs). Macrophages are key actors of both inflammation and its active resolution due to their plastic phenotype. In line with this high plasticity, macrophages can be hijacked by cancer cells to support tumor progression and immune escape, or therapy resistance. Impaired resolution of cancer-associated inflammation supported by TAMs may thus reinforces tumor progression. From this perspective, recent evidence suggests that stimulating macrophage’s pro-resolving functions using SPMs can promote inflammation resolution in cancer and improve anticancer treatments. Thus, TAMs’ re-education toward an antitumor phenotype by using SPMs opens a new line of attack in cancer treatment. Here, we review SPMs’ anticancer capacities with special attention regarding their effects on TAMs. We further discuss how this new therapeutic approach could be envisioned in cancer therapy.
Highlights
Inflammation is recognized as a hallmark of cancer [1] and several lines of evidence have highlighted the significance of chronic inflammation in fueling tumor progression and influencing tumor response to treatment in many cancers
This new inflammatory vision of tumor biology is well supported by numerous studies that have highlighted the main contribution of chronic inflammation in cancer progression [4, 5]
Due to the emerging central role of specialized pro-resolving mediators (SPMs) in inflammation resolution, SPM biology is a trending field of study in human diseases that emerge as potent therapeutic targets in chronic inflammatory diseases and in cancers
Summary
Inflammation is recognized as a hallmark of cancer [1] and several lines of evidence have highlighted the significance of chronic inflammation in fueling tumor progression and influencing tumor response to treatment in many cancers. It has been reported that TAM indirect interactions with lung cancer cells induced SPM production (RvE3, RvD2, RvD5) [66], but to a lower extent than PGs and LTs. To strengthen the switch of bioactive lipid mediators occurring during inflammation resolution, the promotion of SPMs synthesis within tumors would reduce inflammation and restore antitumor functions of macrophages in the TME. New insights in inflammation biology suggest that promoting its active resolution rather than achieving its complete inhibition may help to foster an effective antitumoral immune response, in particular during anticancer treatments [89] In this regard, recent studies demonstrated that SPMs exerted intrinsic antitumor activities mainly through macrophages and greatly improve tumor response to chemotherapies in various murine cancer models [86]. These results underline a SPM-based phenotypic switch in macrophages toward an intermediate phenotype between M1-like and M2like [155, 157, 159] with pro-resolving functions
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