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      Resolution of Cancer-Promoting Inflammation: A New Approach for Anticancer Therapy

      review-article
      1 , 1 , 1 , *
      Frontiers in Immunology
      Frontiers Media S.A.
      inflammation, cancer, lipoxins, resolvins, immunity

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          Abstract

          Inflammation is a protective response that eliminates harmful stimuli and restores tissue homeostasis, whereas the failure to resolve inflammation leads to the development of malignancies. Immune cells in the tumor inflammatory microenvironment endow cancer cells with their specific hallmarks, including mutations, metabolic reprograming, angiogenesis, invasion, and metastasis. Targeting the inflammatory microenvironment with anti-inflammatory drugs (e.g., aspirin) or by enhancing antitumor immunity (e.g., chimeric antigen receptor T cell therapy) has been extensively investigated and has achieved promising results in many cancers. Recently, a novel approach promoting antitumor immunity via a dual anti-inflammatory and pro-resolving strategy was proposed based on the discovery of potent, endogenous, specialized pro-resolving mediators, including lipoxins, resolvins, protectins, and maresins. In this review, we describe the updated principal cellular and molecular mechanisms of inflammation resolution and cancer immunity and discuss the pro-resolution strategy in cancer treatment and prevention.

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          Most cited references53

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          Proresolving lipid mediators and mechanisms in the resolution of acute inflammation.

          Inflammatory responses, like all biological cascades, are shaped by a delicate balance between positive and negative feedback loops. It is now clear that in addition to positive and negative checkpoints, the inflammatory cascade rather unexpectedly boasts an additional checkpoint, a family of chemicals that actively promote resolution and tissue repair without compromising host defense. Indeed, the resolution phase of inflammation is just as actively orchestrated and carefully choreographed as its induction and inhibition. In this review, we explore the immunological consequences of omega-3-derived specialized proresolving mediators (SPMs) and discuss their place within what is currently understood of the role of the arachidonic acid-derived prostaglandins, lipoxins, and their natural C15-epimers. We propose that treatment of inflammation should not be restricted to the use of inhibitors of the acute cascade (antagonism) but broadened to take account of the enormous therapeutic potential of inducers (agonists) of the resolution phase of inflammation.
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            γδ T cells in cancer.

            With the promise of T cell-based therapy for cancer finally becoming reality, this Review focuses on the less-studied γδ T cell lineage and its diverse responses to tumours. γδ T cells have well-established protective roles in cancer, largely on the basis of their potent cytotoxicity and interferon-γ production. Besides this, recent studies have revealed a series of tumour-promoting functions that are linked to interleukin-17-producing γδ T cells. Here, we integrate the current knowledge from both human and mouse studies to highlight the potential of γδ T cell modulation to improve cancer immunotherapy.
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              Abrogation of TGF beta signaling in mammary carcinomas recruits Gr-1+CD11b+ myeloid cells that promote metastasis.

              Aberrant TGFbeta signaling is common in human cancers and contributes to tumor metastasis. Here, we demonstrate that Gr-1+CD11b+ myeloid cells are recruited into mammary carcinomas with type II TGF beta receptor gene (Tgfbr2) deletion and directly promote tumor metastasis. Gr-1+CD11b+ cells infiltrate into the invasive front of tumor tissues and facilitate tumor cell invasion and metastasis through a process involving metalloproteinase activity. This infiltration of Gr-1+CD11b+ cells also results in increased abundance of TGF beta 1 in tumors with Tgfbr2 deletion. The recruitment of Gr-1+CD11b+ cells into tumors with Tgfbr2 deletion involves two chemokine receptor axes, the SDF-1/CXCR4 and CXCL5/CXCR2 axes. Together, these data indicate that Gr-1+CD11b+ cells contribute to TGFbeta-mediated metastasis through enhancing tumor cell invasion and metastasis.
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                Author and article information

                Contributors
                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                02 February 2017
                2017
                : 8
                : 71
                Affiliations
                [1] 1Institute of Cancer, Xinqiao Hospital, Third Military Medical University , Chongqing, China
                Author notes

                Edited by: Fang-Ping Huang, University of Hong Kong, Hong Kong

                Reviewed by: Lidija Klampfer, Albert Einstein College of Medicine, USA; Joanne Lysaght, Trinity College Dublin, Ireland

                *Correspondence: Yongsheng Li, yli@ 123456tmmu.edu.cn

                Specialty section: This article was submitted to Cancer Immunity and Immunotherapy, a section of the journal Frontiers in Immunology

                Article
                10.3389/fimmu.2017.00071
                5288347
                28210259
                9adfd9a2-3d57-4497-8e17-dee5e1b6417e
                Copyright © 2017 Zhang, Zhu and Li.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 25 October 2016
                : 17 January 2017
                Page count
                Figures: 4, Tables: 0, Equations: 0, References: 106, Pages: 11, Words: 7972
                Funding
                Funded by: National Natural Science Foundation of China 10.13039/501100001809
                Award ID: 81472435, 81671573
                Categories
                Immunology
                Review

                Immunology
                inflammation,cancer,lipoxins,resolvins,immunity
                Immunology
                inflammation, cancer, lipoxins, resolvins, immunity

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