Having it both ways: how STAT3 deficiency blocks graft-versus-host disease while preserving graft-versus-leukemia activity
Allogeneic hematopoietic cell transplantation can cure patients with high-risk leukemia through graft-versus-leukemia (GVL) effects, the process by which malignant leukemic cells are cleared by donor-derived immune cells from the graft. The problem of harnessing GVL effects while controlling inflamm...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
| Published: |
American Society for Clinical Investigation
2023-08-01
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| Series: | The Journal of Clinical Investigation |
| Online Access: | https://doi.org/10.1172/JCI172251 |
| _version_ | 1797634428994846720 |
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| author | Joshua D. Brandstadter Riley Outen Ivan Maillard |
| author_facet | Joshua D. Brandstadter Riley Outen Ivan Maillard |
| author_sort | Joshua D. Brandstadter |
| collection | DOAJ |
| description | Allogeneic hematopoietic cell transplantation can cure patients with high-risk leukemia through graft-versus-leukemia (GVL) effects, the process by which malignant leukemic cells are cleared by donor-derived immune cells from the graft. The problem of harnessing GVL effects while controlling inflammation and host-organ damage linked with graft-versus-host disease (GVHD) has been the most formidable hurdle facing allogeneic hematopoietic cell transplantation. This powerful, curative-intent therapy remains among the most toxic treatments in the hematologist’s armamentarium due to the combined risks of GVHD-related morbidity, infections, and leukemia relapse. In this issue of the JCI, Li, Wang, et al. report that T cell Stat3 deficiency can extricate GVL effects from GVHD through tissue-specific programmed death-ligand 1/programmed cell death protein 1–dependent (PD-L1/PD-1-dependent) bioenergetic alterations that blunt harmful T cell effects in GVHD target organs, while preserving their beneficial antitumor activity in lymphohematopoietic tissues. |
| first_indexed | 2024-03-11T12:07:32Z |
| format | Article |
| id | doaj.art-55a4593ef9294378a448ff8d9e716234 |
| institution | Directory Open Access Journal |
| issn | 1558-8238 |
| language | English |
| last_indexed | 2024-03-11T12:07:32Z |
| publishDate | 2023-08-01 |
| publisher | American Society for Clinical Investigation |
| record_format | Article |
| series | The Journal of Clinical Investigation |
| spelling | doaj.art-55a4593ef9294378a448ff8d9e7162342023-11-07T16:20:41ZengAmerican Society for Clinical InvestigationThe Journal of Clinical Investigation1558-82382023-08-0113315Having it both ways: how STAT3 deficiency blocks graft-versus-host disease while preserving graft-versus-leukemia activityJoshua D. BrandstadterRiley OutenIvan MaillardAllogeneic hematopoietic cell transplantation can cure patients with high-risk leukemia through graft-versus-leukemia (GVL) effects, the process by which malignant leukemic cells are cleared by donor-derived immune cells from the graft. The problem of harnessing GVL effects while controlling inflammation and host-organ damage linked with graft-versus-host disease (GVHD) has been the most formidable hurdle facing allogeneic hematopoietic cell transplantation. This powerful, curative-intent therapy remains among the most toxic treatments in the hematologist’s armamentarium due to the combined risks of GVHD-related morbidity, infections, and leukemia relapse. In this issue of the JCI, Li, Wang, et al. report that T cell Stat3 deficiency can extricate GVL effects from GVHD through tissue-specific programmed death-ligand 1/programmed cell death protein 1–dependent (PD-L1/PD-1-dependent) bioenergetic alterations that blunt harmful T cell effects in GVHD target organs, while preserving their beneficial antitumor activity in lymphohematopoietic tissues.https://doi.org/10.1172/JCI172251 |
| spellingShingle | Joshua D. Brandstadter Riley Outen Ivan Maillard Having it both ways: how STAT3 deficiency blocks graft-versus-host disease while preserving graft-versus-leukemia activity The Journal of Clinical Investigation |
| title | Having it both ways: how STAT3 deficiency blocks graft-versus-host disease while preserving graft-versus-leukemia activity |
| title_full | Having it both ways: how STAT3 deficiency blocks graft-versus-host disease while preserving graft-versus-leukemia activity |
| title_fullStr | Having it both ways: how STAT3 deficiency blocks graft-versus-host disease while preserving graft-versus-leukemia activity |
| title_full_unstemmed | Having it both ways: how STAT3 deficiency blocks graft-versus-host disease while preserving graft-versus-leukemia activity |
| title_short | Having it both ways: how STAT3 deficiency blocks graft-versus-host disease while preserving graft-versus-leukemia activity |
| title_sort | having it both ways how stat3 deficiency blocks graft versus host disease while preserving graft versus leukemia activity |
| url | https://doi.org/10.1172/JCI172251 |
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