Research Papers: Autophagy and Cell Death:
The multifaceted role of autophagy in tumor evasion from immune surveillance
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Bassam Janji1, Elodie Viry1, Etienne Moussay1, Jérôme Paggetti1, Tsolère Arakelian1, Takouhie Mgrditchian1, Yosra Messai2, Muhammad Zaeem Noman1,2, Kris Van Moer1, Meriem Hasmim2, Fathia Mami-Chouaib2, Guy Berchem1,3 and Salem Chouaib2
1 Laboratory of Experimental Cancer Research, Department of Oncology, Luxembourg Institute of Health, Luxembourg City, Luxembourg
2 UMR 1186, Gustave Roussy Cancer Campus, Villejuif, France
3 Centre Hospitalier de Luxembourg, Department of Hemato-Oncology, Luxembourg City, Luxembourg
Bassam Janji, email:
Keywords: autophagy, hypoxia, tumor microenvironment, tumor immunity, cancer immunotherapy
Received: October 27, 2015 Accepted: January 06, 2016 Published: February 20, 2016
While autophagy is constitutively executed at basal level in all cells, it is activated in cancer cells in response to various microenvironmental stresses including hypoxia. It is now well established that autophagy can act both as tumor suppressor or tumor promoter. In this regard, several reports indicate that the tumor suppressor function of autophagy is associated with its ability to scavenge damaged oxidative organelles, thereby preventing the accumulation of toxic oxygen radicals and limiting the genome instability. Paradoxically, in developed tumors, autophagy can promote the survival of cancer cells and therefore operates as a cell resistance mechanism. The consensus appears to be that autophagy has a dual role in suppressing tumor initiation and in promoting the survival of established tumors.
This has inspired significant interest in applying anti-autophagy therapies as an entirely new approach to cancer treatment. While much remains to be learned about the regulation and context-dependent biological role of autophagy, it is now well established that modulation of this process could be an attractive approach for the development of novel anticancer therapeutic strategies. In this review, we will summarize recent reports describing how tumor cells, by activating autophagy, manage to resist the immune cell attack. Data described in this review strongly argue that targeting autophagy may represent a conceptual realm for new immunotherapeutic strategies aiming to block the immune escape and therefore providing rational approach to future tumor immunotherapy design.
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