Tumor Niche Network-Defined Subtypes Predict Immunotherapy Response of Esophageal Squamous Cell Cancer.
Tumor Niche Network-Defined Subtypes Predict Immunotherapy Response of Esophageal Squamous Cell Cancer.
复制标题
肿瘤生态位网络定义的亚型预测食管鳞状细胞癌的免疫治疗反应。
DOI：
10.1101/2023.02.15.528539
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Park,Jae-Il
中科院分区：
文献类型：
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作者：
Ko,Kyung-Pil;Zhang,Shengzhe;Huang,Yuanjian;Kim,Bongjun;Zou,Gengyi;Jun,Sohee;Zhang,Jie;Martin,Cecilia;Dunbar,KarenJ;Efe,Gizem;Rustgi,AnilK;Zhang,Haiyang;Nakagawa,Hiroshi;Park,Jae-Il
尽管免疫检查点抑制剂(ICIS)的结果很有希望，但对ICI的耐药性提出了一个新的挑战。因此，为特定的ICI应用选择患者对于最大化治疗效果至关重要。在这里，我们整理了69例人食管鳞癌(ESCC)患者的肿瘤微环境(TME)单细胞转录数据集，以确定ESCC的亚型。对T细胞和髓系细胞的细胞网络和转录特征的综合分析定义了不同的ESCC亚型，其特征是T细胞耗竭，以及白细胞介素性(IL)和干扰素(干扰素)信号。此外，这种方法将ESCC患者分为ICI应答者和无应答者，通过整个肿瘤转录本和抗PD-1 ICI应答者和无应答者的液体活检单细胞转录本验证了这一点。我们的研究基于TME转录网络对ESCC患者进行分层，为ESCC患者的肿瘤生态位重塑提供了新的见解，并潜在地预测了ICI反应。
Despite the promising outcomes of immune checkpoint inhibitors (ICIs), resistance to ICI presents a new challenge. Therefore, selecting patients for specific ICI applications is crucial for maximizing therapeutic efficacy. Herein, we curated 69 human esophageal squamous cell cancer (ESCC) patients' tumor microenvironment (TME) single-cell transcriptomic datasets to subtype ESCC. Integrative analyses of the cellular network and transcriptional signatures of T cells and myeloid cells define distinct ESCC subtypes characterized by T cell exhaustion, and interleukin (IL) and interferon (IFN) signaling. Furthermore, this approach classifies ESCC patients into ICI responders and non-responders, as validated by whole tumor transcriptomes and liquid biopsy-based single-cell transcriptomes of anti-PD-1 ICI responders and non-responders. Our study stratifies ESCC patients based on TME transcriptional network, providing novel insights into tumor niche remodeling and potentially predicting ICI responses in ESCC patients.