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

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

*Corresponding author for this work

Research output: Contribution to journalShort surveypeer-review

47 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 - Apr 2012

Keywords

  • Adaptive immunity
  • Autophagy
  • Cancer vaccines
  • Hypoxia

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