Transplantation tolerance versus immune evasion: Mechanistic divergences and therapeutic frontiers for islet cell replacement
- 1Department of Surgery, Division of Cardiothoracic Surgery, Transplant and Stem Cell Immunobiology (TSI)-Lab, University of California, San Francisco, San Francisco, CA, USA
- 2Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA, USA
- 3Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
Abstract
Allogeneic transplantation is encumbered by the toxicities of chronic immunosuppression, driving innovations for lifelong graft acceptance without ongoing therapy. Transplantation tolerance, a recipient-centric strategy, utilizes central deletional processes through mixed hematopoietic chimerism and thymic repertoire sculpting, complemented by peripheral mechanisms such as T cell anergy, exhaustion, apoptotic deletion, and regulatory T cell dominance. Adjunctive costimulatory blockade enhances the latter pathways, yet tolerance remains precarious, susceptible to destabilization by infections or inflammatory perturbations via heterologous immunity. Conversely, immune evasion adopts a product-centric approach, engineering grafts to intrinsically circumvent adaptive allorejection, innate cytotoxicity, and autoimmune recognition and responses. These mechanistic contrasts—dynamic recipient modulation versus robust graft stealth—underscore immune evasion’s transformative promise and resilience, with empirical validation for cell and organoid transplantation. This review focusses on islet cell replacement therapy, wherein cadaveric allogeneic islet allografts have been clinically available for over four decades, complemented by recent advancements in stem cell-derived islet products.
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BibTeX
@article{deuse2026transplantation,
title = {{Transplantation tolerance versus immune evasion: Mechanistic divergences and therapeutic frontiers for islet cell replacement}},
author = {Tobias Deuse and Sonja Schrepfer},
journal = {Cell Reports Medicine},
year = {2026},
month = jul,
doi = {10.1016/j.xcrm.2026.102888},
url = {https://doi.org/10.1016/j.xcrm.2026.102888},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Transplantation tolerance versus immune evasion: Mechanistic divergences and therapeutic frontiers for islet cell replacement
AU - Tobias Deuse
AU - Sonja Schrepfer
PY - 2026
DA - 2026/07/02
JO - Cell Reports Medicine
DO - 10.1016/j.xcrm.2026.102888
UR - https://doi.org/10.1016/j.xcrm.2026.102888
AB - Allogeneic transplantation is encumbered by the toxicities of chronic immunosuppression, driving innovations for lifelong graft acceptance without ongoing therapy. Transplantation tolerance, a recipient-centric strategy, utilizes central deletional processes through mixed hematopoietic chimerism and thymic repertoire sculpting, complemented by peripheral mechanisms such as T cell anergy, exhaustion, apoptotic deletion, and regulatory T cell dominance. Adjunctive costimulatory blockade enhances the latter pathways, yet tolerance remains precarious, susceptible to destabilization by infections or inflammatory perturbations via heterologous immunity. Conversely, immune evasion adopts a product-centric approach, engineering grafts to intrinsically circumvent adaptive allorejection, innate cytotoxicity, and autoimmune recognition and responses. These mechanistic contrasts—dynamic recipient modulation versus robust graft stealth—underscore immune evasion’s transformative promise and resilience, with empirical validation for cell and organoid transplantation. This review focusses on islet cell replacement therapy, wherein cadaveric allogeneic islet allografts have been clinically available for over four decades, complemented by recent advancements in stem cell-derived islet products.
SN - 2666-3791
ER -