The development of immunologic memory is critical for host defense against pathogens and for anti-cancer immunity, be it spontaneous or induced by check-point blockade or adoptive cell therapies. Although the concept of immunologic memory is old, very recent research has revealed new types of memory cells and layers of complex transcriptional and metabolic control, all of which could also be manipulated in the clinic. This session will focus on the latest research pertaining to the biology of tissue-resident memory T cells, transcriptional control and metabolic regulation of memory T cells, and the biology of memory-like natural killer (NK) cells.
Dr. Thomas Kupper will discuss the biology of tissue-resident memory T cells (TRM), which reside principally in peripheral non-lymphoid barrier tissues that interface with the environment. accumulate in these tissues as a function of time and their primary role is to mediate rapid and specific host defense. Infections in non-barrier tissues (e.g., kidney, brain, pancreas) can also lead to the recruitment of T cells, and a subset of these T cells remain behind as TRM. While TRM can be protective against microbial infection, it is becoming clear that autoimmune and autoinflammatory diseases in many tissues can be mediated by pathogenic TRM. will also discuss the important role these cells play in controlling infection as well as ongoing strategies to suppress and dislodge pathogenic TRM from involved tissues to reduce inflammation.
Dr. Jeffrey Rathmell will focus on how the metabolism of T cells can influence their specification into functionally distinct subsets in immunity and inflammation. Activation of T cells leads to a dramatic reprogramming of cell metabolism that is specific to each subset. The metabolic requirements of each T cell subset are distinct and may provide new approaches to selectively modulate immunity in normal settings as well as in inflammatory diseases or in treatment of cancer. Dr. Rathmell will discuss key nutrients and metabolic pathways that direct T cell subset specification and fate.
Dr. Ananda Goldrath will discuss the transcriptional control of TRM differentiation. CD8+ TRM are optimally positioned at common sites of pathogen exposure, where they elicit rapid and robust antiviral immune responses. However, the molecular signals controlling tissue residency and homeostasis of TRM remain unclear. Furthermore, tumor infiltrating lymphocytes (TIL) share a core TRM transcriptional signature which controls TIL residency. Dr. Goldrath will discuss the identification of novel transcriptional regulators in TRM differentiation and homeostasis by exploiting a dual-screening platform and integrating computational and RNAi in vivo screening approaches. hese findings provide novel insight into the biology of T cell residency, which could be leveraged to enhance vaccine efficacy or adoptive therapy treatments against cancer.
Dr. Todd Fehniger will focus on the biology of NK cells which are innate lymphoid cells that contribute to host antipathogen defense and can mediate anti-tumor responses. While classically considered innate immune cells, NK cells have been shown to “remember” prior activation events, including stimulation by cytokines and viral infection. These experienced NK cells differentiate into innate memory-like or adaptive NK cells. Dr. Fehniger will provide an overview of innate memory-like responses by NK cells, including a current understanding of mechanisms leading to persistent NK cell memory. Furthermore, he will discuss the biology of cytokine-induced memory-like NK cells, their role in enhanced anti-leukemia responses, and use of these cells in early-phase clinical trials as a form of cellular adoptive immunotherapy for leukemia patients.
Thomas Kupper, MD
Jeffrey Rathmell, PhD
Ananda Goldrath, PhD
Todd Fehniger, MD,PhD
Active, International, Emeritus, and Honorary Members
Associate, International Associate, Student, and Resident Members