Macrophage spatial heterogeneity in gastric cancer defined by multiplex immunohistochemistry

• Published in: Nature communications Vol. 10; no. 1; pp. 3928 - 15
• Main Authors: Huang, Yu-Kuan, Wang, Minyu, Sun, Yu, Di Costanzo, Natasha, Mitchell, Catherine, Achuthan, Adrian, Hamilton, John A., Busuttil, Rita A., Boussioutas, Alex
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 02-09-2019; Nature Publishing Group; Nature Portfolio
• Subjects: 13; 13/1; 13/51; 14/34; 45; 45/61; 631/208/69; 631/250/2504/342; 631/67/1504/1829; 631/67/327; 631/67/580; Adult; Aged; Aged, 80 and over; Antigens, CD - genetics; Antigens, CD - metabolism; Antigens, Differentiation, Myelomonocytic - genetics; Antigens, Differentiation, Myelomonocytic - metabolism; B7-H1 Antigen - genetics; B7-H1 Antigen - metabolism; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Cancer; CD163 antigen; Female; Gastric cancer; Gene Expression Profiling; Heterogeneity; Humanities and Social Sciences; Humans; Immunohistochemistry; Immunohistochemistry - methods; Kaplan-Meier Estimate; Macrophages; Macrophages - metabolism; Male; Middle Aged; multidisciplinary; Multiplexing; Multivariate analysis; Receptors, Cell Surface - genetics; Receptors, Cell Surface - metabolism; Science; Science (multidisciplinary); Spatial distribution; Spatial heterogeneity; Stomach Neoplasms - genetics; Stomach Neoplasms - metabolism; Stomach Neoplasms - pathology; Tumor Microenvironment; Tumors
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-019-11788-4

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.
Tumor associated macrophages are functionally and phenotypically heterogeneous. Here the authors describe the spatial distribution of distinct macrophage populations within regions of gastric cancer and probe their associations with clinical outcomes, gene signatures and PDL1 expression.