CanNKC Forum

We would like to start off the year with discussion exploring the inherent ability of NK cells to resist being infected by virus . There are a number of viruses that infect immune cells: eg. HIV infection of CD4 T cells and DCs, influenza or ZIKV infection of macrophages, and EBV infection of B cells, to name a few. However, we are unaware of any wild-type virus capable of productively infecting NK cells. Understanding this broad resistance to viral infection could hold many therapeutic implications. Below are some topics for discussion: 1) Are there any wild-type viruses known to productively infect NK cells? 2) Through what mechanism are NK cells able to broadly evade infection by virus? 3) Could these mechanisms be harnessed in other cell types as an anti-viral therapy? 4) Primary NK cells are also notoriously difficult to transduce efficiently. Could the mechanisms for their resistance to viral infection be targeted to improve transduction efficiency of primary NK cells? Please feel free to discuss these questions and any others you may have about viral infection of NK cells in this section of the forum.

This month we would like to open discussion on NK cell metabolism . There is a growing understanding of the critical role cell metabolism plays in regulating immune cell function. For instance, in T cells and macrophages, it is now understood that modulating cell metabolism is sufficient to determine subset polarization and function. This year in particular, a number of impactful studies have emerged from groups in Europe, the United States, and Asia demonstrating that cell metabolism is integral to NK cell development, education, activation, effector functions, and memory generation. Please see the following links for some selected publications on this topic: Assmann et al. (2017) Nat Immunol: https://www.ncbi.nlm.nih.gov/pubmed/28920951 Schafer et al. (2018) J Allergy Clin Immunol : https://www.ncbi.nlm.nih.gov/pubmed/30096390 Cichocki et al. (2018) J Exp Med: https://www.ncbi.nlm.nih.gov/pubmed/30061358 Loftus et al. (2018) Nat Commun : https://www.ncbi.nlm.nih.gov/pubmed/29904050 Wang et al. (2018) Nat Commun: https://www.ncbi.nlm.nih.gov/pubmed/30451838 Indeed, this developing field holds pivotal implications fundamental to NK cell biology and function, yet many questions remain to be explored. Our questions are as follows: 1) What are important future areas of study on NK cell metabolism? What are current gaps in the literature? 2) What can we do to develop the field of NK cell metabolism in Canada? 3) Are there groups in Canada currently working on NK cell metabolism and if so, what techniques are groups employing to study metabolism? Please feel free to discuss these questions and any others you may have about NK cell metabolism in this section of the forum.

At the Universite de Sherbrooke, we have observed accumulation of fatty acids in NK cells and this altered metabolism impairs their ability to clear tumors in the postoperative period.