Survival of effector CD8+ T cells during influenza infection is dependent on autophagy.

The activation and expansion of effector CD8(+) T cells are essential for controlling viral infections and tumor surveillance. During an immune response, T cells encounter extrinsic and intrinsic factors, including oxidative stress, nutrient availability, and inflammation, that can modulate their capacity to activate, proliferate, and survive. The dependency of T cells on autophagy for in vitro and in vivo activation, expansion, and memory remains unclear.

Autophagy inhibition in cancer therapy: metabolic considerations for antitumor immunity.

Tumors and the immune system are intertwined in a competition where tilting the fine balance between tumor-specific immunity and tolerance can ultimately decide the fate of the host. Defensive and suppressive immunological responses to cancer are exquisitely sensitive to metabolic features of rapidly growing tumors, such as hypoxia, low nutrient availability, and aberrant growth factor signaling. As a result, clinical therapies impacting these properties change the in situ antitumor immune response by virtue of disrupting the tumor environment.

Implications of therapy-induced selective autophagy on tumor metabolism and survival.

Accumulating evidence indicates that therapies designed to trigger apoptosis in tumor cells cause mitochondrial depolarization, nuclear damage, and the accumulation of misfolded protein aggregates, resulting in the activation of selective forms of autophagy. These selective forms of autophagy, including mitophagy, nucleophagy, and ubiquitin-mediated autophagy, counteract apoptotic signals by removing damaged cellular structures and by reprogramming cellular energy metabolism to cope with therapeutic stress. As a result, the efficacies of numerous current cancer therapies may be improved by combining them with adjuvant treatments that exploit or disrupt key metabolic processes induced by selective forms of autophagy.

When Cells Suffocate: Autophagy in Cancer and Immune Cells under Low Oxygen.

Hypoxia is a signature feature of growing tumors. This cellular state creates an inhospitable condition that impedes the growth and function of all cells within the immediate and surrounding tumor microenvironment. To adapt to hypoxia, cells activate autophagy and undergo a metabolic shift increasing the cellular dependency on anaerobic metabolism.