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Measuring Mitochondrial Function of Naïve and Effector CD8 T Cells
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Activated B cells suppress T-cell function through metabolic competition.

Nobuhiko Imahashi1,2, Rafet Basar1, Yuefan Huang3

  • 1Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

Journal for Immunotherapy of Cancer
|December 21, 2022
PubMed
Summary

Activated B cells suppress T-cell immune responses by altering their metabolism, a finding with implications for cancer immunotherapy. These B cells consume oxygen and glucose, impacting T-cell function and potentially hindering anti-tumor immunity.

Keywords:
B-lymphocytesT-lymphocytesimmunomodulationimmunotherapymelanoma

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Area of Science:

  • Immunology
  • Cancer Biology
  • Metabolic Research

Background:

  • B cells are crucial regulators of immune responses.
  • Activated B cells can induce immunosuppression, but the underlying mechanisms remain unclear.

Purpose of the Study:

  • To investigate the role of activated B cell metabolic activity in T-cell suppression.
  • To explore the impact of B cell metabolism on anti-tumor immunity.

Main Methods:

  • In vitro experiments and analysis of clinical samples.
  • Utilized mass cytometry and single-cell RNA sequencing.

Main Results:

  • Activated B cells exhibit an immunoregulatory phenotype, suppressing T cells via metabolic competition.
  • B cells increase oxidative phosphorylation (OXPHOS), inducing T-cell hypoxia, and increase glycolysis, leading to glucose deprivation and lactic acid production.
  • This metabolic reprogramming inhibits the mammalian target of rapamycin (mTOR) pathway in T cells, suppressing their cytokine production and proliferation.
  • Tumor-associated B cells in melanoma patients display high glycolytic and OXPHOS activity, correlating with poor response to immune checkpoint blockade therapy.

Conclusions:

  • Revealed the immunomodulatory effects of activated B cell metabolism on T-cell responses.
  • Highlighted the potential role of B cell immunometabolism in suppressing anti-tumor immunity.
  • Provided novel insights into immunometabolism with implications for cancer immunotherapy.