Immunotherapy for metastatic colorectal cancer is effective only for mismatch repair-deficient tumors with high microsatellite instability that demonstrate immune infiltration, suggesting that tumor cells can determine their immune microenvironment. To understand this cross-talk, we analyzed the transcriptome of 91,103 unsorted single cells from 23 Korean and 6 Belgian patients. Cancer cells displayed transcriptional features reminiscent of normal differentiation programs, and genetic alterations that apparently fostered immunosuppressive microenvironments directed by regulatory T cells, myofibroblasts and myeloid cells. Intercellular network reconstruction supported the association between cancer cell signatures and specific stromal or immune cell populations. Our collective view of the cellular landscape and intercellular interactions in colorectal cancer provide mechanistic information for the design of efficient immuno-oncology treatment strategies.

转移性结直肠癌的免疫疗法仅对具有微卫星不稳定性的失配修复缺陷肿瘤有效，这些肿瘤表现出免疫浸润，表明肿瘤细胞可以确定其免疫微环境。为了了解这种相声，我们分析了来自23名韩国人和6名比利时人的91,103个未分类的单细胞的转录组。癌细胞显示出转录特征，使人联想到正常的分化程序和遗传改变，这些遗传改变显然促进了由调节性T细胞，成肌纤维细胞和髓样细胞定向的免疫抑制微环境。细胞间网络重建支持癌细胞特征与特定基质或免疫细胞群之间的关联。