Mechanisms of Lymphocyte Mediated Cytotoxicity in Health and Disease

Cytotoxic T cells (CTLs) and NK cells are our strongest weapon to fight viral infections and cancer, as strikingly documented by immunoregulatory disorders associated with CTL or NK cell deficiency or dysfunction. Not surprisingly, the cells are exploited for innovative immunotherapeutic strategies, including CAR-based therapy. Since the initial discovery of lytic granules, the killing arsenal of cytotoxic cells has expanded to include the Fas/FasL axis and, more recently, the supramolecular attack particles, a new killing entity consisting of a lytic core surrounded by a glycoprotein shell. How these three types of weapons, and others, cooperate in space and time to kill virally infected and cancer cells is still an open question. Understanding this will provide key elements to help design highly controlled and personalized CTL- or NK cell-based therapies.

Considering their central role in our adaptive immune defenses, viral pathogens and cancer cells have evolved counterattack strategies to disable cytotoxic cells. Elucidating these strategies, that are based on targeting the vulnerable elements of the pathway(s) of cytotoxic cell-mediated killing, is expected not only to further our understanding of the underlying mechanisms, but also to develop our own counterattack.

We welcome Review and Original Research articles focused on, but not limited to, the following topics:

• CTL and NK cell killing strategies
• Target cells mechanisms of resistance to cytotoxic cell attack
• Novel immunotherapeutic strategies to enhance CTL-mediated killing