Macrophage spatial heterogeneity in gastric cancer defined by multiplex immunohistochemistry
Macrophage spatial heterogeneity in gastric cancer defined by multiplex immunohistochemistry
复制标题
胃癌巨噬细胞空间异质性的多重免疫组织化学研究
DOI：
10.1038/s41467-019-11788-4
复制
发表时间：
2019-09-02
影响因子：
16.6
通讯作者：
Boussioutas, Alex
中科院分区：
文献类型：
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作者：
Huang, Yu-Kuan;Wang, Minyu;Boussioutas, Alex
肿瘤相关巨噬细胞（TAM）是胃癌（GC）中最丰富的免疫组分之一，由于其异质性而难以表征。已经使用多种方法来阐明这个问题，然而，由于大多数这些方法的组织破坏性，TAM在原位的空间分布仍然不清楚。在这里，我们探讨肿瘤的背景和TAM异质性之间的关系，通过多重免疫组化56人胃癌病例。使用不同的表达标记物的TAMs，我们报告了七个主要人群之间的肿瘤和非肿瘤组织分布。TAM群体相关基因特征反映了它们的异质性和原位极化。通过单变量分析，而非多变量分析，CD 163+（CD 206-）TAM密度增加伴CD 68高表达与免疫信号传导上调和患者生存期改善相关。仅CD 68和CD 206 + TAM与高PDL 1表达相关。
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.