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Inflammatory abrasion of hematopoietic stem cells: a candidate clue for the post-CAR-T hematotoxicity?

Chimeric antigen receptor T-cell (CAR-T) therapy has shown remarkable effects in treating various hematological malignancies. However, hematotoxicity, specifically neutropenia, thrombocytopenia, and anemia, poses a serious threat to patient prognosis and remains a less focused adverse effect of CAR-...

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Detalles Bibliográficos
Autores principales: Sun, Ting, Li, Dengju, Huang, Liang, Zhu, Xiaojian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10200893/
https://www.ncbi.nlm.nih.gov/pubmed/37223096
http://dx.doi.org/10.3389/fimmu.2023.1141779
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author Sun, Ting
Li, Dengju
Huang, Liang
Zhu, Xiaojian
author_facet Sun, Ting
Li, Dengju
Huang, Liang
Zhu, Xiaojian
author_sort Sun, Ting
collection PubMed
description Chimeric antigen receptor T-cell (CAR-T) therapy has shown remarkable effects in treating various hematological malignancies. However, hematotoxicity, specifically neutropenia, thrombocytopenia, and anemia, poses a serious threat to patient prognosis and remains a less focused adverse effect of CAR-T therapy. The mechanism underlying lasting or recurring late-phase hematotoxicity, long after the influence of lymphodepletion therapy and cytokine release syndrome (CRS), remains elusive. In this review, we summarize the current clinical studies on CAR-T late hematotoxicity to clarify its definition, incidence, characteristics, risk factors, and interventions. Owing to the effectiveness of transfusing hematopoietic stem cells (HSCs) in rescuing severe CAR-T late hematotoxicity and the unignorable role of inflammation in CAR-T therapy, this review also discusses possible mechanisms of the harmful influence of inflammation on HSCs, including inflammatory abrasion of the number and the function of HSCs. We also discuss chronic and acute inflammation. Cytokines, cellular immunity, and niche factors likely to be disturbed in CAR-T therapy are highlighted factors with possible contributions to post-CAR-T hematotoxicity.
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spelling pubmed-102008932023-05-23 Inflammatory abrasion of hematopoietic stem cells: a candidate clue for the post-CAR-T hematotoxicity? Sun, Ting Li, Dengju Huang, Liang Zhu, Xiaojian Front Immunol Immunology Chimeric antigen receptor T-cell (CAR-T) therapy has shown remarkable effects in treating various hematological malignancies. However, hematotoxicity, specifically neutropenia, thrombocytopenia, and anemia, poses a serious threat to patient prognosis and remains a less focused adverse effect of CAR-T therapy. The mechanism underlying lasting or recurring late-phase hematotoxicity, long after the influence of lymphodepletion therapy and cytokine release syndrome (CRS), remains elusive. In this review, we summarize the current clinical studies on CAR-T late hematotoxicity to clarify its definition, incidence, characteristics, risk factors, and interventions. Owing to the effectiveness of transfusing hematopoietic stem cells (HSCs) in rescuing severe CAR-T late hematotoxicity and the unignorable role of inflammation in CAR-T therapy, this review also discusses possible mechanisms of the harmful influence of inflammation on HSCs, including inflammatory abrasion of the number and the function of HSCs. We also discuss chronic and acute inflammation. Cytokines, cellular immunity, and niche factors likely to be disturbed in CAR-T therapy are highlighted factors with possible contributions to post-CAR-T hematotoxicity. Frontiers Media S.A. 2023-05-08 /pmc/articles/PMC10200893/ /pubmed/37223096 http://dx.doi.org/10.3389/fimmu.2023.1141779 Text en Copyright © 2023 Sun, Li, Huang and Zhu https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Sun, Ting
Li, Dengju
Huang, Liang
Zhu, Xiaojian
Inflammatory abrasion of hematopoietic stem cells: a candidate clue for the post-CAR-T hematotoxicity?
title Inflammatory abrasion of hematopoietic stem cells: a candidate clue for the post-CAR-T hematotoxicity?
title_full Inflammatory abrasion of hematopoietic stem cells: a candidate clue for the post-CAR-T hematotoxicity?
title_fullStr Inflammatory abrasion of hematopoietic stem cells: a candidate clue for the post-CAR-T hematotoxicity?
title_full_unstemmed Inflammatory abrasion of hematopoietic stem cells: a candidate clue for the post-CAR-T hematotoxicity?
title_short Inflammatory abrasion of hematopoietic stem cells: a candidate clue for the post-CAR-T hematotoxicity?
title_sort inflammatory abrasion of hematopoietic stem cells: a candidate clue for the post-car-t hematotoxicity?
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10200893/
https://www.ncbi.nlm.nih.gov/pubmed/37223096
http://dx.doi.org/10.3389/fimmu.2023.1141779
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