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Macrophage spatial heterogeneity in gastric cancer defined by multiplex immunohistochemistry

Author

Listed:
  • Yu-Kuan Huang

    (Peter MacCallum Cancer Centre
    The University of Melbourne
    The University of Melbourne)

  • Minyu Wang

    (Peter MacCallum Cancer Centre
    The University of Melbourne
    The University of Melbourne)

  • Yu Sun

    (The University of Melbourne
    The University of Melbourne)

  • Natasha Costanzo

    (Peter MacCallum Cancer Centre)

  • Catherine Mitchell

    (Peter MacCallum Cancer Centre)

  • Adrian Achuthan

    (The University of Melbourne)

  • John A. Hamilton

    (The University of Melbourne
    The University of Melbourne and Western Health)

  • Rita A. Busuttil

    (Peter MacCallum Cancer Centre
    The University of Melbourne
    The University of Melbourne)

  • Alex Boussioutas

    (Peter MacCallum Cancer Centre
    The University of Melbourne
    The University of Melbourne)

Abstract

Tumor-associated macrophages (TAMs), one of the most abundant immune components in gastric cancer (GC), are difficult to characterize due to their heterogeneity. Multiple approaches have been used to elucidate the issue, however, due to the tissue-destructive nature of most of these methods, the spatial distribution of TAMs in situ remains unclear. Here we probe the relationship between tumor context and TAM heterogeneity by multiplex immunohistochemistry of 56 human GC cases. Using distinct expression marker profiles on TAMs, we report seven predominant populations distributed between tumor and non-tumor tissue. TAM population-associated gene signatures reflect their heterogeneity and polarization in situ. Increased density of CD163+ (CD206−) TAMs with concurrent high CD68 expression is associated with upregulated immune-signaling and improved patient survival by univariate, but not multivariate analysis. CD68-only and CD206+ TAMs are correlated with high PDL1 expression.

Suggested Citation

  • Yu-Kuan Huang & Minyu Wang & Yu Sun & Natasha Costanzo & Catherine Mitchell & Adrian Achuthan & John A. Hamilton & Rita A. Busuttil & Alex Boussioutas, 2019. "Macrophage spatial heterogeneity in gastric cancer defined by multiplex immunohistochemistry," Nature Communications, Nature, vol. 10(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-11788-4
    DOI: 10.1038/s41467-019-11788-4
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    Cited by:

    1. Yang Chen & Keren Jia & Yu Sun & Cheng Zhang & Yilin Li & Li Zhang & Zifan Chen & Jiangdong Zhang & Yajie Hu & Jiajia Yuan & Xingwang Zhao & Yanyan Li & Jifang Gong & Bin Dong & Xiaotian Zhang & Jian , 2022. "Predicting response to immunotherapy in gastric cancer via multi-dimensional analyses of the tumour immune microenvironment," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    2. Zhe Li & Ping-Zhao Liang & Li Xu & Xing-Xing Zhang & Ke Li & Qian Wu & Xiao-Feng Lou & Tian-Bing Ren & Lin Yuan & Xiao-Bing Zhang, 2023. "In situ orderly self-assembly strategy affording NIR-II-J-aggregates for in vivo imaging and surgical navigation," Nature Communications, Nature, vol. 14(1), pages 1-14, December.

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