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

ABSTRACT: Allograft 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⁺ T_reg) 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.

SUBMITTER: Barbetta A

PROVIDER: S-EPMC11014454 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature

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

Barbetta Arianna A Rocque Brittany B Bangerth Sarah S Street Kelly K Weaver Carly C Chopra Shefali S Kim Janet J Sher Linda L Gaudilliere Brice B Akbari Omid O Kohli Rohit R Emamaullee Juliet J

Science advances 20240412 15

Allograft 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 ...[more]

PMID: 38608023

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Dataset Information

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

Publications

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

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