title: Hijacker of the Antitumor Immune Response: Autophagy Is Showing Its Worst Facet.
abstract: Macroautophagy (hereafter referred to as autophagy) is a housekeeping process constitutively executed at basal level in all cells to promote cellular homeostasis by regulating organelle and protein turnover. However, autophagy deregulation caused by several stress factors, such as hypoxia, is prevalent in many cancers. It is now well established that autophagy can act as tumor suppressor or tumor promoter depending on tumor type, stage, and genetic context. In developed tumors, autophagy promotes the survival of cancer cells and therefore operates as a cell resistance mechanism. Emerging evidence point to the prominent role of autophagy in disabling the antitumor immune response by multiple overlapping mechanisms leading to tumor escape from immune cell attack mediated by both natural killer cells and cytotoxic T-lymphocytes. Such a role has inspired significant interest in applying anti-autophagy therapies as an entirely new approach to overcome tumor escape from immune surveillance, which constitutes so far a major challenge in developing more effective cancer immunotherapies. In this review, we will summarize recent reports describing how tumor cells, by activating autophagy, manage to hijack the immune system. In particular, we will focus on the emerging role of hypoxia-induced autophagy in shaping the antitumor immune response and in allowing tumor cells to outmaneuver an effective immune response and escape immunosurveillance. In keeping with this, we strongly believe that autophagy represents an attractive future therapeutic target to develop innovative and effective cancer immunotherapeutic approaches.
authors.affiliation: Laboratory of Experimental Cancer Research, Department of Oncology, Luxembourg Institute of Health , Luxembourg City , Luxembourg.
authors.forename: Elodie
authors.initials: E
authors.lastname: Viry
authors.affiliation: Laboratory of Experimental Cancer Research, Department of Oncology, Luxembourg Institute of Health, Luxembourg City, Luxembourg; INSERM U1186, Gustave Roussy Cancer Center, Villejuif, France.
authors.forename: Muhammad Zaeem
authors.initials: MZ
authors.lastname: Noman
authors.affiliation: Laboratory of Experimental Cancer Research, Department of Oncology, Luxembourg Institute of Health , Luxembourg City , Luxembourg.
authors.forename: Tsolère
authors.initials: T
authors.lastname: Arakelian
authors.affiliation: Laboratory of Experimental Cancer Research, Department of Oncology, Luxembourg Institute of Health , Luxembourg City , Luxembourg.
authors.forename: Audrey
authors.initials: A
authors.lastname: Lequeux
authors.affiliation: INSERM U1186, Gustave Roussy Cancer Center , Villejuif , France.
authors.forename: Salem
authors.initials: S
authors.lastname: Chouaib
authors.affiliation: Laboratory of Experimental Cancer Research, Department of Oncology, Luxembourg Institute of Health, Luxembourg City, Luxembourg; Department of Hemato-Oncology, Centre Hospitalier du Luxembourg, Luxembourg City, Luxembourg.
authors.forename: Guy
authors.initials: G
authors.lastname: Berchem
authors.affiliation: Laboratory of Experimental Cancer Research, Department of Oncology, Luxembourg Institute of Health , Luxembourg City , Luxembourg.
authors.forename: Etienne
authors.initials: E
authors.lastname: Moussay
authors.affiliation: Laboratory of Experimental Cancer Research, Department of Oncology, Luxembourg Institute of Health , Luxembourg City , Luxembourg.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Paggetti
authors.affiliation: Laboratory of Experimental Cancer Research, Department of Oncology, Luxembourg Institute of Health , Luxembourg City , Luxembourg.
authors.forename: Bassam
authors.initials: B
authors.lastname: Janji
keywords: Cytotoxic T Lymphocytes; Natural Killer cells; antitumor immune response; autophagy; chloroquine and immunological checkpoint-based immunotherapy; hypoxia; tumor microenvironment