Tissue resident memory T cells (TRM) are enriched in non-lymphoid tissues and represent a formidable barrier against invading pathogens and tumors. TRM are armed with deployment ready effector molecules which combined with their frontline location allows them to be early organizing centers of our immune defense. Despite their autonomous nature, TRM rely on careful collaboration with other immune and non-immune cells located within the barrier organ to exert their superior protective role. Here, we highlight recent studies focusing on cellular interactions that regulate TRM establishment and function. A deeper understanding of these processes is instrumental in designing new means to target TRM for desirable outcomes in infectious diseases, cancers and autoimmunity.
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