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Immunomodulatory Effects of Bendamustine in Hematopoietic Cell Transplantation
SIMPLE SUMMARY: Bendamustine is a chemotherapeutic agent used to treat a variety of cancers. It has recently been used in the context of allogeneic hematopoietic cell transplantation (HCT), a treatment mostly used to treat blood cancers. Given before or after transplantation of donor blood or bone m...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8038415/ https://www.ncbi.nlm.nih.gov/pubmed/33916711 http://dx.doi.org/10.3390/cancers13071702 |
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author | Stokes, Jessica Molina, Megan S. Hoffman, Emely A. Simpson, Richard J. Katsanis, Emmanuel |
author_facet | Stokes, Jessica Molina, Megan S. Hoffman, Emely A. Simpson, Richard J. Katsanis, Emmanuel |
author_sort | Stokes, Jessica |
collection | PubMed |
description | SIMPLE SUMMARY: Bendamustine is a chemotherapeutic agent used to treat a variety of cancers. It has recently been used in the context of allogeneic hematopoietic cell transplantation (HCT), a treatment mostly used to treat blood cancers. Given before or after transplantation of donor blood or bone marrow cells, bendamustine has been shown to reduce the side effects of the transplant, including graft-versus-host disease, where the donated cells attack the recipient’s tissues, while also promoting the anti-cancer effects of the transplant. These are exciting findings and show that bendamustine may be used to influence the immune system, called immunomodulation, in a beneficial manner. We report our research and review the available literature outlining these immunomodulatory effects of bendamustine, in hopes that it will promote further investigations utilizing this agent in allogeneic transplants, ultimately improving patient outcomes. ABSTRACT: Bendamustine (BEN) is a unique alkylating agent with efficacy against a broad range of hematological malignancies, although investigations have only recently started to delve into its immunomodulatory effects. These immunomodulatory properties of BEN in the context of hematopoietic cell transplantation (HCT) are reviewed here. Pre- and post-transplant use of BEN in multiple murine models have consistently resulted in reduced GvHD and enhanced GvL, with significant changes to key immunological cell populations, including T-cells, myeloid derived suppressor cells (MDSCs), and dendritic cells (DCs). Further, in vitro studies find that BEN enhances the suppressive function of MDSCs, skews DCs toward cDC1s, enhances Flt3 expression on DCs, increases B-cell production of IL-10, inhibits STAT3 activation, and suppresses proliferation of T- and B-cells. Overall, BEN has a broad range of immunomodulatory effects that, as they are further elucidated, may be exploited to improve clinical outcomes. As such, clinical trials are currently underway investigating new potential applications of BEN in the setting of allogeneic HCT. |
format | Online Article Text |
id | pubmed-8038415 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-80384152021-04-12 Immunomodulatory Effects of Bendamustine in Hematopoietic Cell Transplantation Stokes, Jessica Molina, Megan S. Hoffman, Emely A. Simpson, Richard J. Katsanis, Emmanuel Cancers (Basel) Review SIMPLE SUMMARY: Bendamustine is a chemotherapeutic agent used to treat a variety of cancers. It has recently been used in the context of allogeneic hematopoietic cell transplantation (HCT), a treatment mostly used to treat blood cancers. Given before or after transplantation of donor blood or bone marrow cells, bendamustine has been shown to reduce the side effects of the transplant, including graft-versus-host disease, where the donated cells attack the recipient’s tissues, while also promoting the anti-cancer effects of the transplant. These are exciting findings and show that bendamustine may be used to influence the immune system, called immunomodulation, in a beneficial manner. We report our research and review the available literature outlining these immunomodulatory effects of bendamustine, in hopes that it will promote further investigations utilizing this agent in allogeneic transplants, ultimately improving patient outcomes. ABSTRACT: Bendamustine (BEN) is a unique alkylating agent with efficacy against a broad range of hematological malignancies, although investigations have only recently started to delve into its immunomodulatory effects. These immunomodulatory properties of BEN in the context of hematopoietic cell transplantation (HCT) are reviewed here. Pre- and post-transplant use of BEN in multiple murine models have consistently resulted in reduced GvHD and enhanced GvL, with significant changes to key immunological cell populations, including T-cells, myeloid derived suppressor cells (MDSCs), and dendritic cells (DCs). Further, in vitro studies find that BEN enhances the suppressive function of MDSCs, skews DCs toward cDC1s, enhances Flt3 expression on DCs, increases B-cell production of IL-10, inhibits STAT3 activation, and suppresses proliferation of T- and B-cells. Overall, BEN has a broad range of immunomodulatory effects that, as they are further elucidated, may be exploited to improve clinical outcomes. As such, clinical trials are currently underway investigating new potential applications of BEN in the setting of allogeneic HCT. MDPI 2021-04-03 /pmc/articles/PMC8038415/ /pubmed/33916711 http://dx.doi.org/10.3390/cancers13071702 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Stokes, Jessica Molina, Megan S. Hoffman, Emely A. Simpson, Richard J. Katsanis, Emmanuel Immunomodulatory Effects of Bendamustine in Hematopoietic Cell Transplantation |
title | Immunomodulatory Effects of Bendamustine in Hematopoietic Cell Transplantation |
title_full | Immunomodulatory Effects of Bendamustine in Hematopoietic Cell Transplantation |
title_fullStr | Immunomodulatory Effects of Bendamustine in Hematopoietic Cell Transplantation |
title_full_unstemmed | Immunomodulatory Effects of Bendamustine in Hematopoietic Cell Transplantation |
title_short | Immunomodulatory Effects of Bendamustine in Hematopoietic Cell Transplantation |
title_sort | immunomodulatory effects of bendamustine in hematopoietic cell transplantation |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8038415/ https://www.ncbi.nlm.nih.gov/pubmed/33916711 http://dx.doi.org/10.3390/cancers13071702 |
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