Resident T cell memory

The recent realization that many T cells within the tissues permanently reside at these sites rather than circulate these and other tissues has radically changed fundamental concepts of T cell memory. The inability to circulate implies that resident memory T cells in contrast to circulating memory T cells form isolated populations in the skin, gut, liver, and other organs. This aspect of tissue-resident memory is conceptually relevant, as it enables these cells in contrast to circulating cells to fully adapt to the conditions of the local environment. We hypothesize that Trm are better adapted than circulating memory cells to induce custom-made responses within the target tissue for optimal protection upon challenge with pathogens or tumor cells. Therefore, we anticipate that Trm can be developed into successful advanced therapy cellular products. The success of checkpoint blockade therapy, such as through the administration of anti-PD1 and anti-CTLA4 antibodies to cancer patients, suggests that recruitment of ‘exhausted’ tumor infiltrating lymphocytes including the tumor-resident Trm compartment into effective anti-tumor responses is feasible. Currently, a lack of knowledge on the potential of Trm hampers the use of these memory T cells in cellular therapies. We aim to improve fundamental insight into resident memory development to enable the future use of Trm in cellular therapies against infection and cancer.