Immunotherapy: Open Access
Open Access
ISSN: 2471-9552
ISSN: 2471-9552
Tsolere Arakelian, Takouhie Mgrditchian, Elodie Viry, Guy Berchem, Bassam Janji, Muhammad Zaeem Noman and Salem Chouaib
Luxembourg Institute of Health, Luxembourg
Gustave Roussy Cancer Center, France
Posters & Accepted Abstracts: Immunother Open Acc
Hypoxia, a common feature of the tumor microenvironment has been widely described as a major contributor to tumor resistance to anti cancer therapies. It has been reported that hypoxic stress in the tumor plays a key role in shielding tumor cells from the immune attack. Indeed, tumor cells acquire the capacity to circumvent immune cell attack and hijack the tumor microenvironment to support their own growth and metastasis. Natural Killer (NK) cells are effectors of the innate immune system, capable of killing cancer cells through the release of the cytotoxic granules containing perforin and Granzyme B. We have recently reported that hypoxia dependent activation of autophagy operates in the tumor as an intrinsic resistance mechanism leading to tumor escape from fully functional cytotoxic T-lymphocytes and NK cells mediated lysis. We provided evidence that targeting autophagy was sufficient to restore NK mediated tumor cell killing under hypoxia in vitro and in vivo by inducing a massive infiltration of NK cells into the tumor bed. The molecular mechanism underlying the infiltration of NK cells in autophagy defective tumors is currently under investigation. Our data argue that targeting autophagy in hypoxic tumors revert the immunosuppressive to immuosupportive tumor microenvironment at least in part for NK cells through the regulation of micro environmental factors involved in the NK cell recruitment. Taken together, this study provides a cutting edge advance in our understanding of the critical role of hypoxia induced autophagy in the impairment of NK mediated tumor cell killing and paves the way for formulating more effective NK based antitumor therapy by combining autophagy inhibitors.
Email: tsolere.arakelian@lih.lu