Single-cell sequencing reveals the landscape of the tumor microenvironment in a skeletal undifferentiated pleomorphic sarcoma patient.
Single-cell sequencing reveals the landscape of the tumor microenvironment in a skeletal undifferentiated pleomorphic sarcoma patient.
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单细胞测序揭示了骨骼未分化多形性肉瘤患者肿瘤微环境的景观。
DOI：
10.3389/fimmu.2022.1019870
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发表时间：
2022
影响因子：
7.3
通讯作者：
Xia, Yuan-Zheng
中科院分区：
文献类型：
--
作者：
Yuan, Liu-Liu;Chen, Zhong;Qin, Jian;Qin, Cheng-Jiao;Bian, Jing;Dong, Rui-Fang;Yuan, Tang-Bo;Xu, Yi-Ting;Kong, Ling-Yi;Xia, Yuan-Zheng
皮肤未分化多形性肉瘤（SUPS）是一种恶性程度高、预后差的侵袭性多形性软组织肉瘤。容易复发和转移。肿瘤微环境（TME）和SUPS的病理生理几乎没有描述。单细胞RNA测序（scRNA-seq）提供了一个以前所未有的分辨率剖析人类疾病景观的机会，特别是在缺乏动物模型的疾病中，如SUPS。我们进行scRNA-seq以分析来自SUPS患者的肿瘤组织和癌旁组织。我们确定了这种SUPS病例中的细胞类型和相应的标记基因。我们进一步表明，CD 8+耗尽的T细胞和Treg高表达PDCD 1、CTLA 4和TIGIT。因此，在这种情况下，PDCD 1、CTLA 4和TIGIT被鉴定为潜在靶标。我们应用非整倍体肿瘤的拷贝数核型分析（CopyKAT）来区分成纤维细胞中的恶性细胞和正常细胞。我们的研究确定了8个恶性成纤维细胞亚群在SUPS不同的基因表达谱。TME中的C1-恶性成纤维细胞和C6-恶性成纤维细胞在肿瘤生长、血管生成、转移和免疫应答中起着至关重要的作用。因此，靶向恶性成纤维细胞可能代表这种SUPS疗法的潜在策略。通过tirelizumab进行干预可实现疾病控制，PD-1的免疫检查点抑制剂（ICI）可被视为SUPS患者的一线选择。总之，scRNA-seq分析为这种SUPS治疗提供了强有力的基础，提高了我们对复杂人类疾病的理解，并可能为未来的个性化医疗提供替代方法。
Skeletal undifferentiated pleomorphic sarcoma (SUPS) is an invasive pleomorphic soft tissue sarcoma with a high degree of malignancy and poor prognosis. It is prone to recur and metastasize. The tumor microenvironment (TME) and the pathophysiology of SUPS are barely described. Single-cell RNA sequencing (scRNA-seq) provides an opportunity to dissect the landscape of human diseases at an unprecedented resolution, particularly in diseases lacking animal models, such as SUPS. We performed scRNA-seq to analyze tumor tissues and paracancer tissues from a SUPS patient. We identified the cell types and the corresponding marker genes in this SUPS case. We further showed that CD8+ exhausted T cells and Tregs highly expressed PDCD1, CTLA4 and TIGIT. Thus, PDCD1, CTLA4 and TIGIT were identified as potential targets in this case. We applied copy number karyotyping of aneuploid tumors (CopyKAT) to distinguish malignant cells from normal cells in fibroblasts. Our study identified eight malignant fibroblast subsets in SUPS with distinct gene expression profiles. C1-malignant Fibroblast and C6-malignant Fibroblast in the TME play crucial roles in tumor growth, angiogenesis, metastasis and immune response. Hence, targeting malignant fibroblasts could represent a potential strategy for this SUPS therapy. Intervention via tirelizumab enabled disease control, and immune checkpoint inhibitors (ICIs) of PD-1 may be considered as the first-line option in patients with SUPS. Taken together, scRNA-seq analyses provided a powerful basis for this SUPS treatment, improved our understanding of complex human diseases, and may afforded an alternative approach for personalized medicine in the future.
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影响因子：
16.6
作者：
Aran D;Camarda R;Odegaard J;Paik H;Oskotsky B;Krings G;Goga A;Sirota M;Butte AJ
通讯作者：
Butte AJ
影响因子：
4.3
作者：
Lall S;Ray S;Bandyopadhyay S
通讯作者：
Bandyopadhyay S
影响因子：
64.8
作者：
Navin N;Kendall J;Troge J;Andrews P;Rodgers L;McIndoo J;Cook K;Stepansky A;Levy D;Esposito D;Muthuswamy L;Krasnitz A;McCombie WR;Hicks J;Wigler M
通讯作者：
Wigler M
影响因子：
3.7
作者：
Liu，Bo;Wei，Hong;Xiao，Xing
通讯作者：
Xiao，Xing
DOI：
10.1002/path.5176
发表时间：
2019-03
期刊：
The Journal of pathology
影响因子：
--
作者：
Ali NM;Niada S;Brini AT;Morris MR;Kurusamy S;Alholle A;Huen D;Antonescu CR;Tirode F;Sumathi V;Latif F
通讯作者：
Latif F