4.5 Article

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

期刊

CANCER SCIENCE
卷 113, 期 1, 页码 41-52

出版社

WILEY
DOI: 10.1111/cas.15186

关键词

B cell leukemia; immune response; regulatory T cell; relapse; Th1

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资金

  1. AMED [JP21ck0106531]
  2. Bristol Myers Squibb
  3. Mochida Memorial Foundation for Medical and Pharmaceutical Research
  4. Mother and Child Health Foundation

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Research analyzed the tumor immune environment in pediatric B cell precursor acute lymphoblastic leukemia, revealing a dynamic shift of T cells from naive to effector subsets during relapse, as well as a T helper 1-polarized immune profile and increased effector regulatory T cells. These findings may contribute to the pathophysiology of recurrent 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 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 naive 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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