The Crosstalk Between Malignant Cells and Tumor-Promoting Immune Cells Relevant to Immunotherapy in Pancreatic Ductal Adenocarcinoma.
The Crosstalk Between Malignant Cells and Tumor-Promoting Immune Cells Relevant to Immunotherapy in Pancreatic Ductal Adenocarcinoma.
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DOI：
10.3389/fcell.2021.821232
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发表时间：
2021
影响因子：
5.5
通讯作者：
Zuo Z
中科院分区：
文献类型：
--
作者：
Liu X;Luo Z;Ren X;Chen Z;Bao X;Zheng J;Zuo Z
背景资料：胰腺导管腺癌（PDAC）由免疫抑制微环境主导，这使得免疫检查点阻断（ICB）通常无反应。了解PDAC形成免疫抑制微环境的机制对于开发新的有效免疫治疗策略非常重要。 研究方法：本研究通过整合PDAC的单细胞RNA测序数据和批量RNA测序数据，全面评估了恶性细胞和免疫细胞之间的细胞间通讯。构建了一个免疫细胞串扰（MIT）评分来预测PDAC患者的生存和治疗反应。在高和低MIT组中评价免疫学特征、富集途径和突变。 结果：PDAC中有大量免疫细胞浸润，主要为促癌免疫细胞。观察到恶性细胞和促肿瘤免疫细胞之间的频繁通信。鉴定了恶性细胞和促肿瘤免疫细胞之间的15个配体-受体对。我们选择在恶性细胞上高度表达的基因来构建恶性肿瘤免疫串扰（MIT）评分。MIT评分与促肿瘤免疫浸润呈正相关。MIT评分高的PDAC患者通常对免疫检查点阻断（ICB）免疫治疗的反应较差。 结论：本研究所鉴定的配体-受体对可能为开发新的免疫治疗策略提供潜在的靶点。建立MIT评分以测量促肿瘤免疫细胞浸润。它可以作为PDAC长期生存的预后指标，以及ICB免疫治疗反应的预测因子。
Background: Pancreatic ductal adenocarcinoma (PDAC) is dominated by an immunosuppressive microenvironment, which makes immune checkpoint blockade (ICB) often non-responsive. Understanding the mechanisms by which PDAC forms an immunosuppressive microenvironment is important for the development of new effective immunotherapy strategies. Methods: This study comprehensively evaluated the cell-cell communications between malignant cells and immune cells by integrative analyses of single-cell RNA sequencing data and bulk RNA sequencing data of PDAC. A Malignant-Immune cell crosstalk (MIT) score was constructed to predict survival and therapy response in PDAC patients. Immunological characteristics, enriched pathways, and mutations were evaluated in high- and low MIT groups. Results: We found that PDAC had high level of immune cell infiltrations, mainly were tumor-promoting immune cells. Frequent communication between malignant cells and tumor-promoting immune cells were observed. 15 ligand-receptor pairs between malignant cells and tumor-promoting immune cells were identified. We selected genes highly expressed on malignant cells to construct a Malignant-Immune Crosstalk (MIT) score. MIT score was positively correlated with tumor-promoting immune infiltrations. PDAC patients with high MIT score usually had a worse response to immune checkpoint blockade (ICB) immunotherapy. Conclusion: The ligand-receptor pairs identified in this study may provide potential targets for the development of new immunotherapy strategy. MIT score was established to measure tumor-promoting immunocyte infiltration. It can serve as a prognostic indicator for long-term survival of PDAC, and a predictor to ICB immunotherapy response.
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