Strategies for Liver Transplantation Tolerance
Liver transplant (LT) recipients require life-long immunosuppression (IS) therapy to preserve allograft function. The risks of chronic IS include an increased frequency of malignancy, infection, renal impairment, and other systemic toxicities. Despite advances in IS, long-term LT outcomes have not b...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/5/2253 |
| _version_ | 1797395469442220032 |
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| author | Filip Cvetkovski J. Mark Hexham Erik Berglund |
| author_facet | Filip Cvetkovski J. Mark Hexham Erik Berglund |
| author_sort | Filip Cvetkovski |
| collection | DOAJ |
| description | Liver transplant (LT) recipients require life-long immunosuppression (IS) therapy to preserve allograft function. The risks of chronic IS include an increased frequency of malignancy, infection, renal impairment, and other systemic toxicities. Despite advances in IS, long-term LT outcomes have not been improved over the past three decades. Standard-of-care (SoC) therapy can, in rare cases, lead to development of operational tolerance that permits safe withdrawal of maintenance IS. However, successful IS withdrawal cannot be reliably predicted and, in current prospective studies, is attempted several years after the transplant procedure, after considerable exposure to the cumulative burden of maintenance therapy. A recent pilot clinical trial in liver tolerance induction demonstrated that peri-transplant immunomodulation, using a regulatory T-cell (Treg) approach, can reduce donor-specific alloreactivity and allow early IS withdrawal. Herein we review protocols for active tolerance induction in liver transplantation, with a focus on identifying tolerogenic cell populations, as well as barriers to tolerance. In addition, we propose the use of novel IS agents to promote immunomodulatory mechanisms favoring tolerance. With numerous IS withdrawal trials underway, improved monitoring and use of novel immunomodulatory strategies will help provide the necessary knowledge to establish an active liver tolerance induction protocol for widespread use. |
| first_indexed | 2024-03-09T00:34:59Z |
| format | Article |
| id | doaj.art-deab99c197004efaaad819fd49ce00ed |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T00:34:59Z |
| publishDate | 2021-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-deab99c197004efaaad819fd49ce00ed2023-12-11T18:15:00ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-02-01225225310.3390/ijms22052253Strategies for Liver Transplantation ToleranceFilip Cvetkovski0J. Mark Hexham1Erik Berglund2Research and Development, ITB-Med AB, 113 66 Stockholm, SwedenResearch and Development, ITB-Med AB, 113 66 Stockholm, SwedenResearch and Development, ITB-Med AB, 113 66 Stockholm, SwedenLiver transplant (LT) recipients require life-long immunosuppression (IS) therapy to preserve allograft function. The risks of chronic IS include an increased frequency of malignancy, infection, renal impairment, and other systemic toxicities. Despite advances in IS, long-term LT outcomes have not been improved over the past three decades. Standard-of-care (SoC) therapy can, in rare cases, lead to development of operational tolerance that permits safe withdrawal of maintenance IS. However, successful IS withdrawal cannot be reliably predicted and, in current prospective studies, is attempted several years after the transplant procedure, after considerable exposure to the cumulative burden of maintenance therapy. A recent pilot clinical trial in liver tolerance induction demonstrated that peri-transplant immunomodulation, using a regulatory T-cell (Treg) approach, can reduce donor-specific alloreactivity and allow early IS withdrawal. Herein we review protocols for active tolerance induction in liver transplantation, with a focus on identifying tolerogenic cell populations, as well as barriers to tolerance. In addition, we propose the use of novel IS agents to promote immunomodulatory mechanisms favoring tolerance. With numerous IS withdrawal trials underway, improved monitoring and use of novel immunomodulatory strategies will help provide the necessary knowledge to establish an active liver tolerance induction protocol for widespread use.https://www.mdpi.com/1422-0067/22/5/2253liver transplantationtolerance inductionimmunosuppression |
| spellingShingle | Filip Cvetkovski J. Mark Hexham Erik Berglund Strategies for Liver Transplantation Tolerance International Journal of Molecular Sciences liver transplantation tolerance induction immunosuppression |
| title | Strategies for Liver Transplantation Tolerance |
| title_full | Strategies for Liver Transplantation Tolerance |
| title_fullStr | Strategies for Liver Transplantation Tolerance |
| title_full_unstemmed | Strategies for Liver Transplantation Tolerance |
| title_short | Strategies for Liver Transplantation Tolerance |
| title_sort | strategies for liver transplantation tolerance |
| topic | liver transplantation tolerance induction immunosuppression |
| url | https://www.mdpi.com/1422-0067/22/5/2253 |
| work_keys_str_mv | AT filipcvetkovski strategiesforlivertransplantationtolerance AT jmarkhexham strategiesforlivertransplantationtolerance AT erikberglund strategiesforlivertransplantationtolerance |