Spatial transcriptomics at single-molecule resolution allows in situ measurements of hundreds to thousands of genes in large areas of tissues, allowing an unprecedented view into the secret life of TRM. Combined with multiparametric immunohistochemistry technologies, these state-of-the-art approaches enable us to understand TRM adaptations in the larger context of their tissue habitat. We are tackling the following questions:
A. Is there a functional design underlying CD8 T cell deployment in tissues?
B. How does intratissue location affect CD8 T cell differentiation and function?
C. What are the environmental conditions that force TRM adaptations?
D. How are these healthy ecosystems changed during infections, tumors, and pathogenic autoimmune reactions?
Combined, we are illuminating the underlying principles that guide CD8 T cell-mediated long-term and robust protection in tissues against infection and tumors.