As two major types of primary liver cancers, the tumor immune microenvironment (TIME) of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) have been well studied separately. However, a systemic assessment of the similarities and differences between the TIME of HCC and ICC is still lacking. In this study, we pictured a landscape of combined TIME of HCC and ICC by sequencing and integrating 41 single-cell RNA-seq samples from four different tissue types of both malignancies. We found that T cells in HCC tumors generally exhibit higher levels of immunosuppression and exhaustion than those in ICC tumors. Myeloid cells in HCC and ICC tumors also exhibit distinct phenotypes and may serve as a key factor driving the differences between their TIMEs. Besides, we identified a cluster of EGR1 macrophages specifically enriched in HCC tumors. Together, our study provides new insights into cellular composition, states and interactions in the TIMEs of HCC and ICC, which could pave the way for the development of future therapeutic targets for liver cancers.

中文翻译：

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肝细胞癌和肝内胆管癌之间不同免疫微环境的特征

作为原发性肝癌的两种主要类型，肝细胞癌（HCC）和肝内胆管癌（ICC）的肿瘤免疫微环境（TIME）已分别得到很好的研究。然而，目前仍缺乏对 HCC 和 ICC TIME 异同的系统评估。在这项研究中，我们通过对来自两种恶性肿瘤四种不同组织类型的 41 个单细胞 RNA-seq 样本进行测序和整合，描绘了 HCC 和 ICC 的组合 TIME 情况。我们发现，HCC 肿瘤中的 T 细胞通常比 ICC 肿瘤中的 T 细胞表现出更高水平的免疫抑制和耗竭。 HCC 和 ICC 肿瘤中的骨髓细胞也表现出不同的表型，可能是驱动其 TIME 差异的关键因素。此外，我们还发现了一组在 HCC 肿瘤中特异性富集的 EGR1 巨噬细胞。总之，我们的研究为 HCC 和 ICC TIME 中的细胞组成、状态和相互作用提供了新的见解，这可能为未来肝癌治疗靶点的开发铺平道路。