Abstract:
:Hematopoietic stem cell transplantation from a haploidentical donor is increasingly used and has become a standard donor option for patients lacking an appropriately matched sibling or unrelated donor. Historically, prohibitive immunological barriers resulting from the high degree of HLA-mismatch included graft-vs.-host disease (GVHD) and graft failure. These were overcome with increasingly sophisticated strategies to manipulate the sensitive balance between donor and recipient immune cells. Three different approaches are currently in clinical use: (a) ex vivo T-cell depletion resulting in grafts with defined immune cell content (b) extensive immunosuppression with a T-cell replete graft consisting of G-CSF primed bone marrow and PBSC (GIAC) (c) T-cell replete grafts with post-transplant cyclophosphamide (PTCy). Intriguing studies have recently elucidated the immunologic mechanisms by which PTCy prevents GVHD. Each approach uniquely affects post-transplant immune reconstitution which is critical for the control of post-transplant infections and relapse. NK-cells play a key role in haplo-HCT since they do not mediate GVHD but can successfully mediate a graft-vs.-leukemia effect. This effect is in part regulated by KIR receptors that inhibit NK cell cytotoxic function when binding to the appropriate HLA-class I ligands. In the context of an HLA-class I mismatch in haplo-HCT, lack of inhibition can contribute to NK-cell alloreactivity leading to enhanced anti-leukemic effect. Emerging work reveals immune evasion phenomena such as copy-neutral loss of heterozygosity of the incompatible HLA alleles as one of the major mechanisms of relapse. Relapse and infectious complications remain the leading causes impacting overall survival and are central to scientific advances seeking to improve haplo-HCT. Given that haploidentical donors can typically be readily approached to collect additional stem- or immune cells for the recipient, haplo-HCT represents a unique platform for cell- and immune-based therapies aimed at further reducing relapse and infections. The rapid advancements in our understanding of the immunobiology of haplo-HCT are therefore poised to lead to iterative innovations resulting in further improvement of outcomes with this compelling transplant modality.
journal_name
Front Immunoljournal_title
Frontiers in immunologyauthors
Baumeister SHC,Rambaldi B,Shapiro RM,Romee Rdoi
10.3389/fimmu.2020.00191subject
Has Abstractpub_date
2020-02-14 00:00:00pages
191issn
1664-3224journal_volume
11pub_type
杂志文章,评审abstract::In gut epithelium, IL-22 transmits signals through STAT3 phosphorylation (pSTAT3) which provides intestinal immunity. Many components in the IL-22-pSTAT3 pathway have been identified as risk factors for inflammatory bowel disease (IBD) and some of them are considered as promising therapeutic targets. However, new pers...
journal_title:Frontiers in immunology
pub_type: 杂志文章
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journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2018.01999
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journal_title:Frontiers in immunology
pub_type: 杂志文章
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journal_title:Frontiers in immunology
pub_type: 杂志文章
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journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2016.00696
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journal_title:Frontiers in immunology
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doi:10.3389/fimmu.2018.00619
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journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2017.00281
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journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2017.01240
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journal_title:Frontiers in immunology
pub_type: 杂志文章
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journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
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journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2018.02595
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abstract::A major obstacle in kidney transplantation for primary focal segmental glomerulosclerosis (FSGS) is the risk of disease recurrence. Recurrent FSGS affects up to 60% of first kidney grafts and exceeds 80% in patients who have lost their first graft due to recurrent FSGS. Clinical and experimental evidence support the h...
journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
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更新日期:2019-07-17 00:00:00
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pub_type: 杂志文章
doi:10.3389/fimmu.2019.02861
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journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2012.00315
更新日期:2012-10-09 00:00:00
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journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2016.00294
更新日期:2016-08-04 00:00:00
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journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2019.02315
更新日期:2019-10-01 00:00:00
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journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
doi:10.3389/fimmu.2018.02423
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pub_type: 杂志文章,评审
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journal_title:Frontiers in immunology
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journal_title:Frontiers in immunology
pub_type: 杂志文章,评审
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journal_title:Frontiers in immunology
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doi:10.3389/fimmu.2017.00115
更新日期:2017-02-14 00:00:00
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pub_type: 杂志文章,评审
doi:10.3389/fimmu.2018.02808
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pub_type: 杂志文章
doi:10.3389/fimmu.2020.570524
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journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2016.00532
更新日期:2016-12-07 00:00:00
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pub_type: 杂志文章
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更新日期:2020-11-24 00:00:00
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journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2015.00144
更新日期:2015-03-30 00:00:00