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Immune microenvironment characteristics in multiple myeloma progression from transcriptome profiling

Multiple myeloma (MM) is characterized by clonal expansion of malignant plasma cells in the bone marrow (BM). Despite the significant advances in treatment, relapsed and refractory MM has not yet been completely cured due to the immune dysfunction in the tumor microenvironment (TME). In this study,...

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Autores principales: Wang, Jin, Hu, Yi, Hamidi, Habib, Dos Santos, Cedric, Zhang, Jingyu, Punnoose, Elizabeth, Li, Wenjin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9413314/
https://www.ncbi.nlm.nih.gov/pubmed/36033464
http://dx.doi.org/10.3389/fonc.2022.948548
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author Wang, Jin
Hu, Yi
Hamidi, Habib
Dos Santos, Cedric
Zhang, Jingyu
Punnoose, Elizabeth
Li, Wenjin
author_facet Wang, Jin
Hu, Yi
Hamidi, Habib
Dos Santos, Cedric
Zhang, Jingyu
Punnoose, Elizabeth
Li, Wenjin
author_sort Wang, Jin
collection PubMed
description Multiple myeloma (MM) is characterized by clonal expansion of malignant plasma cells in the bone marrow (BM). Despite the significant advances in treatment, relapsed and refractory MM has not yet been completely cured due to the immune dysfunction in the tumor microenvironment (TME). In this study, we analyzed the transcriptome data from patients with newly diagnosed (ND) and relapsed/refractory (R/R) MM to characterize differences in the TME and further decipher the mechanism of tumor progression in MM. We observed highly expressed cancer testis antigens and immune suppressive cell infiltration, such as Th2 and M2 cells, are associated with MM progression. Furthermore, the TGF-β signature contributes to the worse outcome of patients with R/R MM. Moreover, patients with ND MM could be classified into immune-low and immune-high phenotypes. Immune-high patients with higher IFN-g signatures are associated with MHC-II–mediated CD4+ T-cell response through CIITA stimulation. The baseline TME status could potentially inform new therapeutic choices for the ND MM who are ineligible for autologous stem cell transplantation and may help predict the response to CAR-T for patients with R/R MM. Our study demonstrates how integrating tumor transcriptome and clinical information to characterize MM immune microenvironment and elucidate potential mechanisms of tumor progression and immune evasion, which will provide insights into MM treatment selection.
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spelling pubmed-94133142022-08-27 Immune microenvironment characteristics in multiple myeloma progression from transcriptome profiling Wang, Jin Hu, Yi Hamidi, Habib Dos Santos, Cedric Zhang, Jingyu Punnoose, Elizabeth Li, Wenjin Front Oncol Oncology Multiple myeloma (MM) is characterized by clonal expansion of malignant plasma cells in the bone marrow (BM). Despite the significant advances in treatment, relapsed and refractory MM has not yet been completely cured due to the immune dysfunction in the tumor microenvironment (TME). In this study, we analyzed the transcriptome data from patients with newly diagnosed (ND) and relapsed/refractory (R/R) MM to characterize differences in the TME and further decipher the mechanism of tumor progression in MM. We observed highly expressed cancer testis antigens and immune suppressive cell infiltration, such as Th2 and M2 cells, are associated with MM progression. Furthermore, the TGF-β signature contributes to the worse outcome of patients with R/R MM. Moreover, patients with ND MM could be classified into immune-low and immune-high phenotypes. Immune-high patients with higher IFN-g signatures are associated with MHC-II–mediated CD4+ T-cell response through CIITA stimulation. The baseline TME status could potentially inform new therapeutic choices for the ND MM who are ineligible for autologous stem cell transplantation and may help predict the response to CAR-T for patients with R/R MM. Our study demonstrates how integrating tumor transcriptome and clinical information to characterize MM immune microenvironment and elucidate potential mechanisms of tumor progression and immune evasion, which will provide insights into MM treatment selection. Frontiers Media S.A. 2022-08-12 /pmc/articles/PMC9413314/ /pubmed/36033464 http://dx.doi.org/10.3389/fonc.2022.948548 Text en Copyright © 2022 Wang, Hu, Hamidi, Dos Santos, Zhang, Punnoose and Li 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 Oncology
Wang, Jin
Hu, Yi
Hamidi, Habib
Dos Santos, Cedric
Zhang, Jingyu
Punnoose, Elizabeth
Li, Wenjin
Immune microenvironment characteristics in multiple myeloma progression from transcriptome profiling
title Immune microenvironment characteristics in multiple myeloma progression from transcriptome profiling
title_full Immune microenvironment characteristics in multiple myeloma progression from transcriptome profiling
title_fullStr Immune microenvironment characteristics in multiple myeloma progression from transcriptome profiling
title_full_unstemmed Immune microenvironment characteristics in multiple myeloma progression from transcriptome profiling
title_short Immune microenvironment characteristics in multiple myeloma progression from transcriptome profiling
title_sort immune microenvironment characteristics in multiple myeloma progression from transcriptome profiling
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9413314/
https://www.ncbi.nlm.nih.gov/pubmed/36033464
http://dx.doi.org/10.3389/fonc.2022.948548
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