Mapping the immune environment in clear cell renal carcinoma by single-cell genomics.
Mapping the immune environment in clear cell renal carcinoma by single-cell genomics.
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DOI：
10.1038/s42003-020-01625-6
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发表时间：
2021-01-27
影响因子：
5.9
通讯作者：
Zhang W
中科院分区：
文献类型：
--
作者：
Borcherding N;Vishwakarma A;Voigt AP;Bellizzi A;Kaplan J;Nepple K;Salem AK;Jenkins RW;Zakharia Y;Zhang W
透明细胞肾细胞癌（ccRCC）是免疫学上最独特的肿瘤类型之一，这是由于对免疫疗法的高应答率，尽管肿瘤突变负荷低。为了表征ccRCC的肿瘤免疫微环境，我们应用单细胞RNA测序（SCRS）沿着T细胞受体（TCR）测序，以绘制来自3名ccRCC患者的匹配肿瘤和血液中的25，688个单个CD45+淋巴和骨髓细胞的转录组异质性。我们还纳入了来自其他四个人的11，367个免疫细胞，这些免疫细胞来自肾脏和外周血，以便于识别和评估ccRCC特异性差异。与正常肾组织相比，肿瘤浸润免疫细胞中的CD8+ T细胞和巨噬细胞群体总体增加。我们进一步证明了肿瘤浸润性CD8+ T细胞的不同细胞转录状态，并确定了MKI 67+增殖亚群是ccRCC进展的潜在罪魁祸首。使用SCRS基因表达，我们发现通过亚群分配优先预测临床结果和病理疾病。通过进一步的表征和功能验证，我们的研究结果可能揭示某些免疫细胞亚群适合治疗干预。Borcherding和Vishwakarma等人使用单细胞RNA和T细胞受体测序表征了未经治疗的透明细胞肾癌患者的肿瘤免疫微环境。他们发现CD8 + T细胞和巨噬细胞在肿瘤组织中富集，并确定了增殖的CD8 + T细胞群，这可能与抗癌反应有关。
Clear cell renal cell carcinoma (ccRCC) is one of the most immunologically distinct tumor types due to high response rate to immunotherapies, despite low tumor mutational burden. To characterize the tumor immune microenvironment of ccRCC, we applied single-cell-RNA sequencing (SCRS) along with T-cell-receptor (TCR) sequencing to map the transcriptomic heterogeneity of 25,688 individual CD45+ lymphoid and myeloid cells in matched tumor and blood from three patients with ccRCC. We also included 11,367 immune cells from four other individuals derived from the kidney and peripheral blood to facilitate the identification and assessment of ccRCC-specific differences. There is an overall increase in CD8+ T-cell and macrophage populations in tumor-infiltrated immune cells compared to normal renal tissue. We further demonstrate the divergent cell transcriptional states for tumor-infiltrating CD8+ T cells and identify a MKI67 + proliferative subpopulation being a potential culprit for the progression of ccRCC. Using the SCRS gene expression, we found preferential prediction of clinical outcomes and pathological diseases by subcluster assignment. With further characterization and functional validation, our findings may reveal certain subpopulations of immune cells amenable to therapeutic intervention. Borcherding and Vishwakarma et al. characterize the tumor immune microenvironment in treatment-naïve clear cell renal carcinoma patients using single-cell RNA- and T-cell receptor sequencing. They find CD8 + T cells and macrophages are enriched in tumor tissue, and identify a proliferative CD8 + T-cell population, which may be relevant for anti-cancer responses.
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影响因子：
8.8
作者：
Baldan, V.;Griffiths, R.;Hawkins, R. E.;Gilham, D. E.
通讯作者：
Gilham, D. E.
影响因子：
7.4
作者：
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通讯作者：
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影响因子：
11.5
作者：
Giraldo, Nicolas A.;Becht, Etienne;Sautes-Fridman, Catherine
通讯作者：
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影响因子：
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作者：
Baine MK;Turcu G;Zito CR;Adeniran AJ;Camp RL;Chen L;Kluger HM;Jilaveanu LB
通讯作者：
Jilaveanu LB
影响因子：
5.6
作者：
Borcherding N;Kolb R;Gullicksrud J;Vikas P;Zhu Y;Zhang W
通讯作者：
Zhang W