title: Hypoxia-induced autophagy: a new player in cancer immunotherapy?
abstract: A major challenge in formulating an effective immunotherapy is to overcome the mechanisms of tumor escape from immunosurveillance. We showed that hypoxia-induced autophagy impairs cytotoxic T-lymphocyte (CTL)-mediated tumor cell lysis by regulating phospho-STAT3 in target cells. Autophagy inhibition in hypoxic cells decreases phospho-STAT3 and restores CTL-mediated tumor cell killing by a mechanism involving the ubiquitin proteasome system and SQSTM1/p62. Simultaneously boosting the CTL-response, using a TRP-peptide vaccination strategy, and targeting autophagy in hypoxic tumors, improves the efficacy of cancer vaccines and promotes tumor regression in vivo. Overall, in addition to its immunosuppressive effect, the hypoxic microenvironment also contributes to immunoresistance and can be detrimental to antitumor effector cell functions.
authors.affiliation: Unité INSERM U753, Institut Gustave Roussy, Villejuif, France.
authors.forename: Muhammad Zaeem
authors.initials: MZ
authors.lastname: Noman
authors.forename: Bassam
authors.initials: B
authors.lastname: Janji
authors.forename: Guy
authors.initials: G
authors.lastname: Berchem
authors.forename: Fathia
authors.initials: F
authors.lastname: Mami-Chouaib
authors.forename: Salem
authors.initials: S
authors.lastname: Chouaib
mesh_terms: D000818:Animals; D001343:Autophagy; D015687:Cell Hypoxia; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007167:Immunotherapy; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D009369:Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D059016:Tumor Microenvironment
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D050796:STAT3 Transcription Factor