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Non-lymphoid organs, in mice and humans, contain CD8 + tissue-resident memory T (T RM ) cells. They play important roles in tissue homoeostasis as well as defence against infections and cancer. T RM cells have common characteristics that enables their tissue residency and function. However, the wide variety of tissues, some with continually exposure to invading microbes, distinct organ structures and functions, impose tissue-specific differences on T RM cells. Upon tissue-entry, they need to adapt to local circumstances by modifying their transcriptional machinery, enabling interactions with the - often specialised - surrounding cells and available metabolites. Heterogeneity amongst T RM cells may have implications for their defence function, organ-specific autoimmunity and chronic immune disorders. Here we indicate shared and unique T RM cell features within different tissues to provide a better understanding of their function and discuss possible future research directions., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)