@article{4eaa4ab85470473ab71931064d381607,
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.",
keywords = "Adaptive immunity, Autophagy, Cancer vaccines, Hypoxia",
author = "Noman, {Muhammad Zaeem} and Bassam Janji and Guy Berchem and Fathia Mami-Chouaib and Salem Chouaib",
note = "Funding Information: simultaneous boosting of the immune It has become increasingly clear that the the way to formulate more effective cancer system and inhibition of autophagy in tumor microenvironment plays a crucial vaccine-based therapy. While several clini-spontaneous animal tumor models. role in the control of immune protection cal trials using the autophagy inhibitor Transgenic mouse models of spontaneous and contains many overlapping mecha-hydroxychloroquine in combination with oncogene-driven tumors that are deficient nisms, which ultimately lead to tumor several chemotherapy drugs are currently in autophagy could be useful to explore evasion of antigen-specific immuno-in progress, trials combining peptide the impact of the hypoxic tumor micro-therapy. Obviously, tumors have evolved vaccination with autophagy inhibitors environment and autophagy inhibition to utilize hypoxic stress to their own could be an innovative strategy in cancer on the antitumor immune responses. advantage by activating key biochemical immunotherapy. Integrating clinical and Nevertheless, our results strongly argue that and cellular pathways that are important lab findings will be crucial to understand in vivo inhibition of autophagy potentiates for progression, namely survival and the complex role of hypoxia-induced the antitumor effect of a TRP2-based metastasis. In this regard, we provided autophagy in modulating host tumor vaccine. It would be interesting to investi-evidence that hypoxia-induced autophagy immunity. gate whether the inhibition of autophagy plays a determinant role in tumor evasion will affect other parameters of the anti-of specific CTL-mediated lysis. Further- tumor T cell activity in vivo and in vitro more, our findings establish, for the first This work was supported by grants from (i.e., cytokine production, proliferation, time, that simultaneously boosting the the ARC (Association pour la Recherche activation, etc.). Several other important immune system and inhibiting autophagy sur le Cancer), Ligue contre le Cancer, mediators of immune tolerance such as can enhance the therapeutic efficacy of INCA (Institut National du Cancer), the number of the myeloid-derived antigen-based cancer vaccines. This study FNR (Fonds National de la Recherche,",
year = "2012",
month = apr,
doi = "10.4161/auto.19572",
language = "English",
volume = "8",
pages = "704--706",
journal = "Autophagy",
issn = "1554-8627",
publisher = "Landes Bioscience",
number = "4",
}