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Nat Commun. 2019 Sep 2;10(1):3928. doi: 10.1038/s41467-019-11788-4.

Macrophage spatial heterogeneity in gastric cancer defined by multiplex immunohistochemistry.

Author information

1
Upper Gastrointestinal Translational Research Laboratory, Peter MacCallum Cancer Centre, Melbourne, Victoria, 3000, Australia.
2
Sir Peter MacCallum Department of Oncology, The University of Melbourne, Victoria, 3010, Australia.
3
Department of Medicine, Royal Melbourne Hospital, The University of Melbourne, Victoria, 3010, Australia.
4
Department of Pathology, Peter MacCallum Cancer Centre, Melbourne, Victoria, 3000, Australia.
5
The Australian Institute for Musculoskeletal Science (AIMSS), The University of Melbourne and Western Health, St. Albans, Victoria, 3021, Australia.
6
Upper Gastrointestinal Translational Research Laboratory, Peter MacCallum Cancer Centre, Melbourne, Victoria, 3000, Australia. alex.boussioutas@petermac.org.
7
Sir Peter MacCallum Department of Oncology, The University of Melbourne, Victoria, 3010, Australia. alex.boussioutas@petermac.org.
8
Department of Medicine, Royal Melbourne Hospital, The University of Melbourne, Victoria, 3010, Australia. alex.boussioutas@petermac.org.

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.

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