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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...

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Autores principales: Guo, Hao, Yang, Jingyi, Wang, Haoran, Liu, Xingchen, Liu, Yanyan, Zhou, Keshu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
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.
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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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