Metabolomic profiling of tumor-infiltrating macrophages during tumor growth

Naoki Umemura, Masahiro Sugimoto, Yusuke Kitoh, Masanao Saio, Hiroshi Sakagami

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)

Abstract

Myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs) are both key immunosuppressive cells that contribute to tumor growth. Metabolism and immunity of tumors depend on the tumor microenvironment (TME). However, the intracellular metabolism of MDSCs and TAMs during tumor growth remains unclear. Here, we characterized CD11b+ cells isolated from a tumor-bearing mouse model to compare intratumoral TAMs and intrasplenic MDSCs. Intratumoral CD11b+ cells and intrasplenic CD11b+ cells were isolated from tumor-bearing mice at early and late stages (14 and 28 days post-cell transplantation, respectively). The cell number of intrasplenic CD11b+ significantly increased with tumor growth. These cells included neutrophils holding segmented leukocytes or monocytes with an oval nucleus and Gr-1hi IL-4Rαhi cells without immunosuppressive function against CD8 T cells. Thus, these cells were classified as MDSC-like cells (MDSC-LCs). Intratumoral CD11b+ cells included macrophages with a round nucleus and were F4/80hi Gr-1lo IL-4Rαhi cells. Early stage intratumoral CD11b+ cells inhibited CD8 T cells via TNFα. Thus, this cell population was classified as TAMs. Metabolomic analyses of intratumoral TAMs and MDSC-LCs during tumor growth were conducted. Metabolic profiles of intratumoral TAMs showed larger changes in various metabolic pathways, e.g., glycolysis, TCA cycle, and glutamic acid pathways, during tumor growth compared with MDSL-LCs. Our findings demonstrated that intratumoral TAMs showed an immunosuppressive capacity from the early tumor stage and underwent intracellular metabolism changes during tumor growth. These results clarify the intracellular metabolism of TAMs during tumor growth and contribute to our understanding of tumor immunity.

Original languageEnglish
Pages (from-to)2357-2369
Number of pages13
JournalCancer Immunology, Immunotherapy
Volume69
Issue number11
DOIs
Publication statusPublished - 2020 Nov 1

Keywords

  • Metabolomics
  • Myeloid derived suppressor cells
  • Tumor infiltrating macrophages
  • Tumor necrosis factor-alpha

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Cancer Research

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