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Reshaping the tumor microenvironment: The versatility of immunomodulatory drugs in B-cell neoplasms
Immunomodulatory drugs (IMiDs) such as thalidomide, lenalidomide and pomalidomide are antitumor compounds that have direct tumoricidal activity and indirect effects mediated by multiple types of immune cells in the tumor microenvironment (TME). IMiDs have shown remarkable therapeutic efficacy in a s...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9596992/ https://www.ncbi.nlm.nih.gov/pubmed/36311747 http://dx.doi.org/10.3389/fimmu.2022.1017990 |
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author | Guo, Hao Yang, Jingyi Wang, Haoran Liu, Xingchen Liu, Yanyan Zhou, Keshu |
author_facet | Guo, Hao Yang, Jingyi Wang, Haoran Liu, Xingchen Liu, Yanyan Zhou, Keshu |
author_sort | Guo, Hao |
collection | PubMed |
description | Immunomodulatory drugs (IMiDs) such as thalidomide, lenalidomide and pomalidomide are antitumor compounds that have direct tumoricidal activity and indirect effects mediated by multiple types of immune cells in the tumor microenvironment (TME). IMiDs have shown remarkable therapeutic efficacy in a set of B-cell neoplasms including multiple myeloma, B-cell lymphomas and chronic lymphocytic leukemia. More recently, the advent of immunotherapy has revolutionized the treatment of these B-cell neoplasms. However, the success of immunotherapy is restrained by immunosuppressive signals and dysfunctional immune cells in the TME. Due to the pleiotropic immunobiological properties, IMiDs have shown to generate synergetic effects in preclinical models when combined with monoclonal antibodies, immune checkpoint inhibitors or CAR-T cell therapy, some of which were successfully translated to the clinic and lead to improved responses for both first-line and relapsed/refractory settings. Mechanistically, despite cereblon (CRBN), an E3 ubiquitin ligase, is considered as considered as the major molecular target responsible for the antineoplastic activities of IMiDs, the exact mechanisms of action for IMiDs-based TME re-education remain largely unknown. This review presents an overview of IMiDs in regulation of immune cell function and their utilization in potentiating efficacy of immunotherapies across multiple types of B-cell neoplasms. |
format | Online Article Text |
id | pubmed-9596992 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-95969922022-10-27 Reshaping the tumor microenvironment: The versatility of immunomodulatory drugs in B-cell neoplasms Guo, Hao Yang, Jingyi Wang, Haoran Liu, Xingchen Liu, Yanyan Zhou, Keshu Front Immunol Immunology Immunomodulatory drugs (IMiDs) such as thalidomide, lenalidomide and pomalidomide are antitumor compounds that have direct tumoricidal activity and indirect effects mediated by multiple types of immune cells in the tumor microenvironment (TME). IMiDs have shown remarkable therapeutic efficacy in a set of B-cell neoplasms including multiple myeloma, B-cell lymphomas and chronic lymphocytic leukemia. More recently, the advent of immunotherapy has revolutionized the treatment of these B-cell neoplasms. However, the success of immunotherapy is restrained by immunosuppressive signals and dysfunctional immune cells in the TME. Due to the pleiotropic immunobiological properties, IMiDs have shown to generate synergetic effects in preclinical models when combined with monoclonal antibodies, immune checkpoint inhibitors or CAR-T cell therapy, some of which were successfully translated to the clinic and lead to improved responses for both first-line and relapsed/refractory settings. Mechanistically, despite cereblon (CRBN), an E3 ubiquitin ligase, is considered as considered as the major molecular target responsible for the antineoplastic activities of IMiDs, the exact mechanisms of action for IMiDs-based TME re-education remain largely unknown. This review presents an overview of IMiDs in regulation of immune cell function and their utilization in potentiating efficacy of immunotherapies across multiple types of B-cell neoplasms. Frontiers Media S.A. 2022-10-12 /pmc/articles/PMC9596992/ /pubmed/36311747 http://dx.doi.org/10.3389/fimmu.2022.1017990 Text en Copyright © 2022 Guo, Yang, Wang, Liu, Liu and Zhou 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 Guo, Hao Yang, Jingyi Wang, Haoran Liu, Xingchen Liu, Yanyan Zhou, Keshu Reshaping the tumor microenvironment: The versatility of immunomodulatory drugs in B-cell neoplasms |
title | Reshaping the tumor microenvironment: The versatility of immunomodulatory drugs in B-cell neoplasms |
title_full | Reshaping the tumor microenvironment: The versatility of immunomodulatory drugs in B-cell neoplasms |
title_fullStr | Reshaping the tumor microenvironment: The versatility of immunomodulatory drugs in B-cell neoplasms |
title_full_unstemmed | Reshaping the tumor microenvironment: The versatility of immunomodulatory drugs in B-cell neoplasms |
title_short | Reshaping the tumor microenvironment: The versatility of immunomodulatory drugs in B-cell neoplasms |
title_sort | reshaping the tumor microenvironment: the versatility of immunomodulatory drugs in b-cell neoplasms |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9596992/ https://www.ncbi.nlm.nih.gov/pubmed/36311747 http://dx.doi.org/10.3389/fimmu.2022.1017990 |
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