Human mucosal tissue-resident memory T cells in health and disease

Memory T cells are fundamental to maintain immune surveillance of the human body. During the past decade, it has become apparent that non-recirculating resident memory T cells (TRMs) form a first line memory response in tissues to tackle re-infections. The fact that TRMs are essential for local immunity highlights the therapeutic potential of targeting this population against tumors and infections. However, similar to other immune subsets, TRMs are heterogenous and may form distinct effector populations with unique functions at diverse tissue sites. Further insight into the mechanisms of how TRM function and respond to pathogens and malignancies at different mucosal sites will help to shape future vaccine and immunotherapeutic approaches. Here, we review the current understanding of TRM function and biology at four major mucosal sites: gastrointestinal tract, lung, head and neck, as well as female reproductive tract. We also summarize our current knowledge of how TRM targets invading pathogens and developing tumor cells at these mucosal sites and contemplate how TRMs may be exploited to protect from infections and cancer.