Spatially resolved immune exhaustion within the alloreactive microenvironment predicts liver transplant rejection-Reference-Cited by-同舟云学术

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

Published:2024-04-12 Issue:15 Volume:10 Page:
ISSN:2375-2548
Container-title:Science Advances
language:en
Short-container-title:Sci. Adv.

Author:

Barbetta Arianna¹^ORCID,Rocque Brittany¹,Bangerth Sarah¹^ORCID,Street Kelly²^ORCID,Weaver Carly³,Chopra Shefali⁴,Kim Janet¹,Sher Linda¹,Gaudilliere Brice⁵^ORCID,Akbari Omid⁶⁷^ORCID,Kohli Rohit³⁸^ORCID,Emamaullee Juliet¹⁶⁸^ORCID

Affiliation:

1. Division of Abdominal Organ Transplantation and Hepatobiliary Surgery, Department of Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.

2. Division of Biostatistics, Department of Population and Public Health, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.

3. Division of Gastroenterology, Hepatology and Nutrition, Children’s Hospital Los Angeles, Los Angeles, CA, USA.

4. Department of Pathology, University of Southern California, Los Angeles, CA, USA.

5. Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA, USA.

6. Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.

7. Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.

8. Division of Abdominal Organ Transplantation, Children’s Hospital Los Angeles, Los Angeles, CA, USA.

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.

Publisher

American Association for the Advancement of Science (AAAS)

Link

https://www.science.org/doi/pdf/10.1126/sciadv.adm8841

Reference69 articles.

1. Incidence and Severity of Acute Cellular Rejection in Recipients Undergoing Adult Living Donor or Deceased Donor Liver Transplantation

2. The natural history of acute histologic rejection without biochemical graft dysfunction in orthotopic liver transplantation: A systematic review

3. Acute Rejection Increases Risk of Graft Failure and Death in Recent Liver Transplant Recipients

4. Cyclosporin versus tacrolimus for liver transplanted patients;Haddad E. M.;Cochrane Database Syst. Rev.,2006

5. Banff Schema for grading liver allograft rejection: An international consensus document;Demetris A. J.;Hepatology,1997

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