Function and regulation of tissue memory-resident
cd8+ t cells
Although the mechanisms of CD8+ T cell activation by antigen presenting cells (APC) in lymph nodes and CD8+ T cell recruitment to the tumor site are well understood, our knowledge on the regulation of CD8+ T cell at the tumor site remains limited.
We investigate the role of a subpopulation of CD8+ T cells, the Tissue Resident-Memory (TRM) T cells, in breast and lung cancers. TRM T cells are non-recirculating T cells that reside in peripheral tissues. They are aptly localized to survey tissues and trigger a rapid local immune response. However, their ability to kill cancer cells is still poorly understood in Humans. Furthermore, we do not know how TRM survival is regulated in tissues and how/by which APC they are activated to perform their functions. The objectives of this project are to: i) Define the function of TRM in tumors and adjacent healthy tissues; ii) Analyze TRM/ APC interactions and their functions; iii) Define the effect of immunotherapy treatments on TRM/APC interactions. iv) Discover new therapeutic strategies to enhance TRM responses in cancer.
We are using and developing 3-dimensional tissue imaging and analysis techniques to functionally map the interactions between TRM and APC directly in tissues (Figure 1) in patients with breast and lung cancers.
This work is performed in close collaboration with clinicians from the IUCT and the Toulouse University Hospital.
Figure 1 : 3-dimensional visualization of human tissue.
Fragment of breast tumor made optically transparent (left) and labeled (right) for MHC-II (gray), CD103 (red), CD8 (green) and DAPI (blue).