Upper Gastrointestinal Translational Research Laboratory, Peter MacCallum Cancer Centre, Melbourne, Victoria, 3000, Australia.
Sir Peter MacCallum Department of Oncology, The University of Melbourne, Victoria, 3010, Australia.
Nat Commun. 2019 Sep 2;10(1):3928. 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.
肿瘤相关巨噬细胞（TAMs）是胃癌（GC）中最丰富的免疫成分之一，由于其异质性，难以进行特征描述。已经使用了多种方法来阐明这个问题，但是，由于大多数这些方法都具有组织破坏性，TAMs 在原位的空间分布仍然不清楚。在这里，我们通过对 56 个人类 GC 病例进行多重免疫组织化学染色来探究肿瘤背景与 TAM 异质性之间的关系。使用 TAMs 上不同的表达标记物特征，我们报告了在肿瘤组织和非肿瘤组织之间分布的七个主要群体。TAM 群体相关的基因特征反映了它们在原位的异质性和极化。CD163+（CD206-）TAMs 的密度增加伴随着 CD68 表达的增加，与上调的免疫信号相关，并通过单因素但不是多因素分析与患者生存改善相关。仅 CD68 和 CD206+TAMs 与高 PD-L1 表达相关。
