Unraveling how tissue-resident memory T cells arise

Suppressing molecular regulator Eomes could be an important strategy to direct developing T cells toward tissue-resident memory T cells (Trm). Klaas van Gisbergen and his team published this in Science Immunology. This could be applied to increase the amount of Trm at the tumor site for the purpose of immunotherapy for cancer patients.  

Our immune system provides protection against the development of tumors. In recent years, it has been shown that tissue-resident memory T cells (Trm) are important immune cells with the ability to clear tumor cells. These Trm develop locally within the tumor site, where they will permanently stay to optimally support anti-tumor immune responses. In order to develop immunotherapies that employ Trm to counter tumor growth, it is essential to understand how these memory T cells can be expanded in vivo or in vitro, but, currently, it is unclear where, when and how Trm develop.  

Therefore, we designed an in vivo mouse model that allowed us to specifically visualize Trm using a fluorescent marker that exclusively labels Trm, but not circulating T cell lineages. Using this model system, we were able to trace the developmental pathway of Trm that is initiated in draining lymph nodes and is completed in the peripheral tissues, where tumors arise.  

We discovered that Trm almost completely separated from circulating T cell lineages at early stages of the immune response. Characterization of these early Trm precursors showed that they lacked an important molecular regulator known as Eomes.  

Interestingly, Eomes could suppress the development of Trm precursors and their offspring. Therefore, Eomes appears to be an important factor that steers developing T cells into the direction of circulating memory T cells rather than Trm.  

Our findings suggest that targeting of Eomes might be an important strategy to increase the number of Trm at the tumor site for the purpose of immunotherapy of cancer patients.  


Hobit identifies TRM precursors that are regulated by Eomes
Loreto Parga-Vidal*, Felix M. Behr*, Natasja A. M. Kragten, Benjamin Nota, Thomas H. Wesselink, Inga Kavazović, Laura E. Covill, Margo B. P. Schuller, Yenan T. Bryceson, Felix M. Wensveen, Rene A. W. van Lier, Teunis J. P. van Dam, Regina Stark, and Klaas P. J. M. van Gisbergen 

*contributed equally