Hypoxia-induced autophagy: A new player in cancer immunotherapy?

Muhammad Zaeem Noman, Bassam Janji, Guy Berchem, Fathia Mami-Chouaib, Salem Chouaib

    Research output: Contribution to journalShort surveypeer-review

    55 Citations (Scopus)

    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.

    Original languageEnglish
    Pages (from-to)704-706
    Number of pages3
    JournalAutophagy
    Volume8
    Issue number4
    DOIs
    Publication statusPublished - 1 Jan 2012

    Keywords

    • Adaptive immunity
    • Autophagy
    • Cancer vaccines
    • Hypoxia

    Cite this