The 21kD GTPase Rac is an evolutionarily ancient regulator of cell shape and behavior. Rac2 is predominantly expressed in hematopoietic cells where it is essential for survival and motility. The hyperactivating mutation Rac2^E62K also causes human immunodeficiency, although the mechanism remains unexplained. Here, we report that in Drosophila, hyperactivating Rac stimulates ovarian cells to cannibalize neighboring cells, destroying the tissue. We then show that hyperactive Rac2^E62K stimulates human HL60-derived macrophage-like cells to engulf and kill living T cell leukemia cells. Primary mouse Rac2^+/E62K bone-marrow-derived macrophages also cannibalize primary Rac2^+/E62K T cells due to a combination of macrophage hyperactivity and T cell hypersensitivity to engulfment. Additionally, Rac2^+/E62K macrophages non-autonomously stimulate wild-type macrophages to engulf T cells. Rac2^E62K also enhances engulfment of target cancer cells by chimeric antigen receptor-expressing macrophages (CAR-M) in a CAR-dependent manner. We propose that Rac-mediated cell cannibalism may contribute to Rac2^+/E62K human immunodeficiency and enhance CAR-M cancer immunotherapy.

This article, collaboratively written by the presidents of the National Latina/o Psychological Association (NLPA), presents leadership as conceptualized and practiced in NLPA. We first identify key leadership constructs in the available literature as well as relevant cultural values, describe liderazgo (leadership) through cultural lenses, and articulate the connections to counseling psychology and the social justice underpinnings that have guided NLPA’s formation and development. We then present a number of events and decisions to illustrate how we have operationalized these organizing principles in both the daily management and long-term goals of NLPA. We conclude with a discussion of the future paths and possible directions in the next decade for the organization.