MEF2C regulates NK cell effector functions through control of lipid metabolism.

Natural killer (NK) cells are a critical first line of defense against viral infection. Rare mutations in a small subset of transcription factors can result in decreased NK cell numbers and function in humans, with an associated increased susceptibility to viral infection. However, our understanding of the specific transcription factors governing mature human NK cell function is limited. Here we use a non-viral CRISPR-Cas9 knockout screen targeting genes encoding 31 transcription factors differentially expressed during human NK cell development. We identify myocyte enhancer factor 2C (MEF2C) as a master regulator of human NK cell functionality ex vivo. MEF2C-haploinsufficient patients and mice displayed defects in NK cell development and effector function, with an increased susceptibility to viral infection. Mechanistically, MEF2C was required for an interleukin (IL)-2- and IL-15-mediated increase in lipid content through regulation of sterol regulatory element-binding protein (SREBP) pathways. Supplementation with oleic acid restored MEF2C-deficient and MEF2C-haploinsufficient patient NK cell cytotoxic function. Therefore, MEF2C is a critical orchestrator of NK cell antiviral immunity by regulating SREBP-mediated lipid metabolism.

The lived experiences of patients with cancer during the COVID-19 pandemic: a qualitative study.

Background: The objective of this study was to explore the impact of COVID-19 on the lived experiences of patients with cancer in Lebanon. Methods: We adopted a descriptive phenomenological approach. We included adults who had been diagnosed with cancer before the pandemic and undergoing treatment at the American University of Beirut Medical Centre. We conducted virtual, semi-structured in-depth interviews with either video or audio recordings. Two team members coded the transcripts independently and identified common themes and patterns. Results: We recruited 11 participants for the study. The analysis identified the following six themes: perceived seriousness of COVID-19, fear of COVID-19 versus fear of cancer, coping mechanisms, treatment availability and accessibility, compliance with public health and social measures and precautionary measures in the healthcare system. The coping mechanisms included staying positive, seeking normalcy, using family support, religiosity and fatalism. Conclusion: Faced with many challenges during the COVID-19 pandemic, patients with cancer resorted to a range of coping strategies.