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Alteration of the immune environment in bone marrow from children with recurrent B cell precursor acute lymphoblastic leukemia

Due to the considerable success of cancer immunotherapy for leukemia, the tumor immune environment has become a focus of intense research; however, there are few reports on the dynamics of the tumor immune environment in leukemia. Here, we analyzed the tumor immune environment in pediatric B cell pr...

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Autores principales: Mikami, Takashi, Kato, Itaru, Wing, James Badger, Ueno, Hiroo, Tasaka, Keiji, Tanaka, Kuniaki, Kubota, Hirohito, Saida, Satoshi, Umeda, Katsutsugu, Hiramatsu, Hidefumi, Isobe, Tomoya, Hiwatari, Mitsuteru, Okada, Ai, Chiba, Kenichi, Shiraishi, Yuichi, Tanaka, Hiroko, Miyano, Satoru, Arakawa, Yuki, Oshima, Koichi, Koh, Katsuyoshi, Adachi, Souichi, Iwaisako, Keiko, Ogawa, Seishi, Sakaguchi, Shimon, Takita, Junko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8748249/
https://www.ncbi.nlm.nih.gov/pubmed/34716967
http://dx.doi.org/10.1111/cas.15186
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author Mikami, Takashi
Kato, Itaru
Wing, James Badger
Ueno, Hiroo
Tasaka, Keiji
Tanaka, Kuniaki
Kubota, Hirohito
Saida, Satoshi
Umeda, Katsutsugu
Hiramatsu, Hidefumi
Isobe, Tomoya
Hiwatari, Mitsuteru
Okada, Ai
Chiba, Kenichi
Shiraishi, Yuichi
Tanaka, Hiroko
Miyano, Satoru
Arakawa, Yuki
Oshima, Koichi
Koh, Katsuyoshi
Adachi, Souichi
Iwaisako, Keiko
Ogawa, Seishi
Sakaguchi, Shimon
Takita, Junko
author_facet Mikami, Takashi
Kato, Itaru
Wing, James Badger
Ueno, Hiroo
Tasaka, Keiji
Tanaka, Kuniaki
Kubota, Hirohito
Saida, Satoshi
Umeda, Katsutsugu
Hiramatsu, Hidefumi
Isobe, Tomoya
Hiwatari, Mitsuteru
Okada, Ai
Chiba, Kenichi
Shiraishi, Yuichi
Tanaka, Hiroko
Miyano, Satoru
Arakawa, Yuki
Oshima, Koichi
Koh, Katsuyoshi
Adachi, Souichi
Iwaisako, Keiko
Ogawa, Seishi
Sakaguchi, Shimon
Takita, Junko
author_sort Mikami, Takashi
collection PubMed
description Due to the considerable success of cancer immunotherapy for leukemia, the tumor immune environment has become a focus of intense research; however, there are few reports on the dynamics of the tumor immune environment in leukemia. Here, we analyzed the tumor immune environment in pediatric B cell precursor acute lymphoblastic leukemia by analyzing serial bone marrow samples from nine patients with primary and recurrent disease by mass cytometry using 39 immunophenotype markers, and transcriptome analysis. High‐dimensional single‐cell mass cytometry analysis elucidated a dynamic shift of T cells from naïve to effector subsets, and clarified that, during relapse, the tumor immune environment comprised a T helper 1‐polarized immune profile, together with an increased number of effector regulatory T cells. These results were confirmed in a validation cohort using conventional flow cytometry. Furthermore, RNA transcriptome analysis identified the upregulation of immune‐related pathways in B cell precursor acute lymphoblastic leukemia cells during relapse, suggesting interaction with the surrounding environment. In conclusion, a tumor immune environment characterized by a T helper 1‐polarized immune profile, with an increased number of effector regulatory T cells, could contribute to the pathophysiology of recurrent B cell precursor acute lymphoblastic leukemia. This information could contribute to the development of effective immunotherapeutic approaches against B cell precursor acute lymphoblastic leukemia relapse.
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spelling pubmed-87482492022-01-14 Alteration of the immune environment in bone marrow from children with recurrent B cell precursor acute lymphoblastic leukemia Mikami, Takashi Kato, Itaru Wing, James Badger Ueno, Hiroo Tasaka, Keiji Tanaka, Kuniaki Kubota, Hirohito Saida, Satoshi Umeda, Katsutsugu Hiramatsu, Hidefumi Isobe, Tomoya Hiwatari, Mitsuteru Okada, Ai Chiba, Kenichi Shiraishi, Yuichi Tanaka, Hiroko Miyano, Satoru Arakawa, Yuki Oshima, Koichi Koh, Katsuyoshi Adachi, Souichi Iwaisako, Keiko Ogawa, Seishi Sakaguchi, Shimon Takita, Junko Cancer Sci Original Articles Due to the considerable success of cancer immunotherapy for leukemia, the tumor immune environment has become a focus of intense research; however, there are few reports on the dynamics of the tumor immune environment in leukemia. Here, we analyzed the tumor immune environment in pediatric B cell precursor acute lymphoblastic leukemia by analyzing serial bone marrow samples from nine patients with primary and recurrent disease by mass cytometry using 39 immunophenotype markers, and transcriptome analysis. High‐dimensional single‐cell mass cytometry analysis elucidated a dynamic shift of T cells from naïve to effector subsets, and clarified that, during relapse, the tumor immune environment comprised a T helper 1‐polarized immune profile, together with an increased number of effector regulatory T cells. These results were confirmed in a validation cohort using conventional flow cytometry. Furthermore, RNA transcriptome analysis identified the upregulation of immune‐related pathways in B cell precursor acute lymphoblastic leukemia cells during relapse, suggesting interaction with the surrounding environment. In conclusion, a tumor immune environment characterized by a T helper 1‐polarized immune profile, with an increased number of effector regulatory T cells, could contribute to the pathophysiology of recurrent B cell precursor acute lymphoblastic leukemia. This information could contribute to the development of effective immunotherapeutic approaches against B cell precursor acute lymphoblastic leukemia relapse. John Wiley and Sons Inc. 2021-11-29 2022-01 /pmc/articles/PMC8748249/ /pubmed/34716967 http://dx.doi.org/10.1111/cas.15186 Text en © 2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Original Articles
Mikami, Takashi
Kato, Itaru
Wing, James Badger
Ueno, Hiroo
Tasaka, Keiji
Tanaka, Kuniaki
Kubota, Hirohito
Saida, Satoshi
Umeda, Katsutsugu
Hiramatsu, Hidefumi
Isobe, Tomoya
Hiwatari, Mitsuteru
Okada, Ai
Chiba, Kenichi
Shiraishi, Yuichi
Tanaka, Hiroko
Miyano, Satoru
Arakawa, Yuki
Oshima, Koichi
Koh, Katsuyoshi
Adachi, Souichi
Iwaisako, Keiko
Ogawa, Seishi
Sakaguchi, Shimon
Takita, Junko
Alteration of the immune environment in bone marrow from children with recurrent B cell precursor acute lymphoblastic leukemia
title Alteration of the immune environment in bone marrow from children with recurrent B cell precursor acute lymphoblastic leukemia
title_full Alteration of the immune environment in bone marrow from children with recurrent B cell precursor acute lymphoblastic leukemia
title_fullStr Alteration of the immune environment in bone marrow from children with recurrent B cell precursor acute lymphoblastic leukemia
title_full_unstemmed Alteration of the immune environment in bone marrow from children with recurrent B cell precursor acute lymphoblastic leukemia
title_short Alteration of the immune environment in bone marrow from children with recurrent B cell precursor acute lymphoblastic leukemia
title_sort alteration of the immune environment in bone marrow from children with recurrent b cell precursor acute lymphoblastic leukemia
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8748249/
https://www.ncbi.nlm.nih.gov/pubmed/34716967
http://dx.doi.org/10.1111/cas.15186
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