Journal
AUTOPHAGY
Volume 9, Issue 3, Pages 317-327Publisher
TAYLOR & FRANCIS INC
DOI: 10.4161/auto.22923
Keywords
IFN1@; autophagy; apoptosis; immunotherapy; chronic myeloid leukemia
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Funding
- National Natural Sciences Foundation of China [30973234, 31171328]
- University of Pittsburgh
- National Institutes of Health [R01CA160417]
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IFN1@ (interferon, type 1, cluster, also called IFN alpha) has been extensively studied as a treatment for patients with chronic myeloid leukemia (CML). The mechanism of anticancer activity of IFN1@ is complex and not well understood. Here, we demonstrate that autophagy, a mechanism of cellular homeostasis for the removal of dysfunctional organelles and proteins, regulates IFN1@-mediated cell death. IFN1@ activated the cellular autophagic machinery in immortalized or primary CML cells. Activation of JAK1-STAT1 and RELA signaling were required for IFN1@-induced expression of BECN1, a key regulator of autophagy. Moreover, pharmacological and genetic inhibition of autophagy enhanced IFN1@-induced apoptosis by activation of the CASP8-BID pathway. Taken together, these findings provide evidence for an important mechanism that links autophagy to immunotherapy in leukemia.
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