| First Author | Houbaert D | Year | 2024 |
| Journal | Cell Rep | Volume | 43 |
| Issue | 4 | Pages | 114020 |
| PubMed ID | 38554280 | Mgi Jnum | J:348068 |
| Mgi Id | MGI:7627916 | Doi | 10.1016/j.celrep.2024.114020 |
| Citation | Houbaert D, et al. (2024) An autophagy program that promotes T cell egress from the lymph node controls responses to immune checkpoint blockade. Cell Rep 43(4):114020 |
| abstractText | Lymphatic endothelial cells (LECs) of the lymph node (LN) parenchyma orchestrate leukocyte trafficking and peripheral T cell dynamics. T cell responses to immunotherapy largely rely on peripheral T cell recruitment in tumors. Yet, a systematic and molecular understanding of how LECs within the LNs control T cell dynamics under steady-state and tumor-bearing conditions is lacking. Intravital imaging combined with immune phenotyping shows that LEC-specific deletion of the essential autophagy gene Atg5 alters intranodal positioning of lymphocytes and accrues their persistence in the LNs by increasing the availability of the main egress signal sphingosine-1-phosphate. Single-cell RNA sequencing of tumor-draining LNs shows that loss of ATG5 remodels niche-specific LEC phenotypes involved in molecular pathways regulating lymphocyte trafficking and LEC-T cell interactions. Functionally, loss of LEC autophagy prevents recruitment of tumor-infiltrating T and natural killer cells and abrogates response to immunotherapy. Thus, an LEC-autophagy program boosts immune-checkpoint responses by guiding systemic T cell dynamics. |
