The untold story of IFN-γ in cancer biology

Interferon (IFN)-γ is the uppermost cytokine implicated in anti-tumor immunity. With its cytostatic, pro-apoptotic and immune-provoking effects, IFN-γ plays a central role in the recognition and elimination of transformed cells. Considering well-characterized anti-tumor effects of this cytokine, many clinical trials and immunotherapy approaches have been designed to reinforce IFN-γ-mediated immunity for different types of cancer. However, the outcomes were not satisfactory and leaded to questioning of alternative actions of IFN-γ. Many regulatory pathways can be induced by IFN-γ to protect the normal tissues from collateral damage and to facilitate the re-establishment of homeostasis. Nevertheless, malignant cells can take the advantage of IFN-γ as an inducer of mediators inhibiting anti-tumor immune reactions. In addition, under the influence of tumor-derived factors, certain types of immune cells are also licensed by IFN-γ to perform regulatory actions. This review focuses on the immune modulatory functions of IFN-γ in cancer as an alternative story to be told.     

“Ciliophagy”: The consumption of cilia components by autophagy

Chronic obstructive pulmonary disease (COPD) involves aberrant airway inflammatory responses to cigarette smoke (CS) associated with respiratory epithelial cell cilia shortening and impaired mucociliary clearance (MCC). The underlying cellular and molecular mechanisms for CS-associated cilia shortening have remained incompletely understood. We have previously demonstrated increased autophagy in the lungs of COPD patients; however, whether or not this process is selective for specific autophagic targets in the lung was not elucidated. Based on observations that increased morphological and biochemical indicators of autophagy correlate with cilia shortening in our models, we posited that autophagy might regulate cilia length in response to CS in the lung. We demonstrate that CS-induced cilia shortening occurs through an autophagy-dependent mechanism mediated by the deacetylase HDAC6 (histone deacetylase 6). Autophagy-impaired (Becn1^+/−, map1lc3b^−/−, or Hdac6^-/Y) mice resist CS-induced cilia shortening. Furthermore, cilia components are identified as autophagic substrates during CS exposure. Assessment of airway cilia function using a 3D MCC assay demonstrates that Becn1^+/−, map1lc3b^−/−, and Hdac6^-/Y mice or mice injected with the HDAC6 inhibitor tubastatin A are protected from CS-associated mucociliary dysfunction. We concluded that an autophagy-dependent pathway regulates cilia length during CS exposure, which identifies new pathways and targets in COPD.     

Artophagy: The art of autophagy—Macroautophagy

Many of us have sketched (by hand or on the computer) depictions of macroautophagy; however, how often have we considered which elements in the drawing are key to illustrating the process? These types of illustrations are easily modified and/or discarded. On the other hand, if you plan to depict the process of macroautophagy in a more permanent medium you need to be more thoughtful about the composition. What items must be included? How should they be situated? What should be the size of each component? Here, we consider one example of an artist’s approach to depicting macroautophagy in a mixed-medium sculpture.     

p53: The Janus of autophagy?

The autophagy pathway functions in adaptation to nutrient stress and tumour suppression. The p53 tumour suppressor, previously thought to positively regulate autophagy, may also inhibit it. This dual interplay between p53 and autophagy regulation is enigmatic, but may underlie key aspects of metabolism and cancer biology.