Tissue-specific anti-tumor NK cell subsets identified in colorectal cancer liver metastases express candidate therapeutic targets

This record contains processed data related to article Tissue-specific anti-tumor NK cell subsets identified in colorectal cancer liver metastases express candidate therapeutic targets Abstract Liver metastases are relatively resistant to checkpoint blockade immunotherapy. The hepatic tissue has distinctive features including high numbers of NK cells. It was therefore important to conduct in depth single-cell analysis of NK cells in colorectal cancer liver metastases (CRLMs) with the effort to dissect their diversity and to identify candidate therapeutic targets. By combining unbiased single-cell transcriptomic with multiparametric flow cytometry analysis, we identified an abundant family of intrahepatic CD56Bright NK cells in CRLMs endowed with anti-tumor functions resulting from specific transcriptional liver programs. Intrahepatic CD56Bright and CD56Dim NK lymphocytes expressed unique transcription factors (IRF8, TOX2), high level of chemokines, and targetable immune checkpoints (ICs), including CXCR4 and the IL-1 receptor family member IL-1R8. CXCR4 pharmacological blocking and an anti-IL-1R8 mAb enhanced the effector function of CRLM NK cells. Targeting the diversity of liver NK cells and their distinct immune-checkpoint repertoires is key to optimize the current immune-therapy protocols in CRLM. Experimental design Single-cell RNA sequencing (scRNA-seq) was performed on samples collected from three colorectal-liver metastasis patients. For each patient, matched samples were obtained from invasive margin (IM, n = 3) and core-tumor adjacent tissue regions (peri-tumor, n = 3) of the liver tumor, as well as from peripheral blood (n = 3).scRNA-seq was performed on flow cytometry-sorted NK cells (Lin-CD56+, excluding CD3+ lymphocytes, myeloid and B cells), as well as on matched flow cytometry-sorted NK cells from PBMCs本数据集收录了与《结直肠癌肝转移灶中鉴定的组织特异性抗肿瘤NK细胞亚群表达候选治疗靶点》相关的经处理后数据。 摘要 肝转移灶对免疫检查点阻断疗法相对耐受。肝脏组织具有诸多独特特征，其中包含大量自然杀伤（NK）细胞。因此，针对结直肠癌肝转移（CRLMs）灶中的NK细胞开展深入的单细胞分析，以解析其多样性并鉴定候选治疗靶点，具有重要研究意义。 本研究结合无偏单细胞转录组测序与多参数流式细胞术分析，在结直肠癌肝转移灶中鉴定出一类丰度较高的肝内CD56Bright NK细胞，该类细胞凭借特异性肝脏转录程序获得了抗肿瘤功能。 肝内CD56Bright与CD56Dim NK淋巴细胞表达独特的转录因子（IRF8、TOX2）、高水平趋化因子，以及可靶向的免疫检查点（immune checkpoints，简称ICs），包括CXCR4与白细胞介素-1受体家族成员IL-1R8。 CXCR4的药物阻断处理与抗IL-1R8单克隆抗体，可增强结直肠癌肝转移灶NK细胞的效应功能。靶向肝脏NK细胞的多样性及其独特的免疫检查点表达谱，是优化结直肠癌肝转移灶当前免疫治疗方案的关键所在。 实验设计 本研究对3名结直肠癌肝转移患者的样本开展单细胞RNA测序（single-cell RNA sequencing，简称scRNA-seq）。每名患者的样本分别采集自肝脏肿瘤的侵袭边缘（IM，n=3）、肿瘤核心旁组织区域（瘤周组织，n=3）以及外周血（n=3）。 本研究对经流式细胞术分选的NK细胞（Lin-CD56+，排除CD3+淋巴细胞、髓系细胞与B细胞），以及外周血单个核细胞（peripheral blood mononuclear cells，简称PBMCs）中匹配的流式分选NK细胞开展单细胞RNA测序。