Spatially resolved immune exhaustion within the alloreactive microenvironment predicts liver transplant rejection

Sci Adv. 2024 Apr 12;10(15):eadm8841. doi: 10.1126/sciadv.adm8841. Epub 2024 Apr 12.ABSTRACTAllograft rejection is common following clinical organ transplantation, but defining specific immune subsets mediating alloimmunity has been elusive. Calcineurin inhibitor dose escalation, corticosteroids, and/or lymphocyte depleting antibodies have remained the primary options for treatment of clinical rejection episodes. Here, we developed a highly multiplexed imaging mass cytometry panel to study the immune response in archival biopsies from 79 liver transplant (LT) recipients with either no rejection (NR), acute T cell-mediated rejection (TCMR), or chronic rejection (CR). This approach generated a spatially resolved proteomic atlas of 461,816 cells (42 phenotypes) derived from 96 pathologist-selected regions of interest. Our analysis revealed that regulatory (HLADR+ Treg) and PD1+ T cell phenotypes (CD4+ and CD8+ subsets), combined with variations in M2 macrophage polarization, were a unique signature of active TCMR. These data provide insights into the alloimmune microenvironment in clinical LT, including identification of potential targets for focused immunotherapy during rejection episodes and suggestion of a substantial role for immune exhaustion in TCMR.PMID:38608023 | DOI:10.1126/sciadv.adm8841
Source: Adv Data - Category: Epidemiology Authors: Source Type: research