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, may 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.This article is protected by copyright. All rights reserved.
About The Expert
Takashi Mikami
Itaru Kato
James Badger Wing
Hiroo Ueno
Keiji Tasaka
Kuniaki Tanaka
Hirohito Kubota
Satoshi Saida
Katsutsugu Umeda
Hidefumi Hiramatsu
Tomoya Isobe
Mitsuteru Hiwatari
Ai Okada
Kenichi Chiba
Yuichi Shiraishi
Hiroko Tanaka
Satoru Miyano
Yuki Arakawa
Koichi Oshima
Katsuyoshi Koh
Souichi Adachi
Keiko Iwaisako
Seishi Ogawa
Shimon Sakaguchi
Junko Takita
References
PubMed