Cell-mediated autophagy promotes cancer cell survival

Cancer Res. 2012 Jun 15;72(12):2970-9. doi: 10.1158/0008-5472.CAN-11-3396. Epub 2012 Apr 13.


Immune effector cells integrate signals that define the nature and magnitude of the subsequent response. Experimental measures for immune cell-mediated lysis of tumors or virally infected targets rely on average responses of permeability or apoptotic changes within a population of targets. Here, we examined individual target cells following interaction with lymphoid effectors. We found that human peripheral blood lymphocytes not only provide lytic signals but also promote autophagy in the remaining cells. At high effector-to-target ratios, autophagy was induced in several human tumors, as assessed by induction of LC3 puncta and diminished p62. Natural killer cells are a primary mediator of this process. In addition, target cell autophagy was enhanced by provision of interleukin (IL)-2, whereas IL-10 attenuated this effect, and cell-to-cell contact strongly enhanced lymphocyte-mediated autophagy. Although IFN-γ can induce autophagy in target cells, IFN-α acted directly on the targets or in concert with lymphocytes to diminish target autophagy in some cell types. Importantly, cell-mediated autophagy promoted resistance from treatment modalities designed to eradicate tumor cells. Our findings therefore show that the lymphocyte-induced cell-mediated autophagy promotes cancer cell survival and may represent an important target for development of novel therapies.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adaptor Proteins, Signal Transducing / biosynthesis
  • Autophagy*
  • Cell Communication
  • Cell Line, Tumor
  • Cell Survival
  • Colonic Neoplasms / immunology*
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / pathology
  • Cytotoxicity, Immunologic*
  • Humans
  • Interferon-alpha / immunology
  • Interferon-gamma / immunology
  • Interleukin-10 / immunology
  • Interleukin-2 / immunology
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / metabolism
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / metabolism
  • Microtubule-Associated Proteins / biosynthesis
  • Pancreatic Neoplasms / immunology*
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology
  • Sequestosome-1 Protein
  • Urinary Bladder Neoplasms / immunology*
  • Urinary Bladder Neoplasms / metabolism
  • Urinary Bladder Neoplasms / pathology


  • Adaptor Proteins, Signal Transducing
  • Interferon-alpha
  • Interleukin-2
  • MAP1LC3A protein, human
  • Microtubule-Associated Proteins
  • SQSTM1 protein, human
  • Sequestosome-1 Protein
  • Interleukin-10
  • Interferon-gamma