研究概要
我们的研究结果表明,BC UDCs可能作为TME的替代物,并可作为治疗性生物标志物。
中文摘要
由于膀胱肿瘤与尿液接触,尿源性细胞(UDCs)可能作为监测膀胱癌(BC)肿瘤微环境(TME)的替代指标。然而,UDCs的组成及其反映肿瘤的程度仍表征不足。我们首次对BC患者UDCs及其配对的肿瘤和外周血单个核细胞(PBMC)进行了单细胞RNA测序。BC尿液比健康供者(HD)尿液细胞更多,除肿瘤细胞和基质细胞外,还包含多种免疫细胞群,包括髓系细胞、CD4+和CD8+ T细胞、自然杀伤(NK)细胞、B细胞和树突状细胞(DCs)。免疫UDCs在转录水平上比血液更接近肿瘤。UDCs包含细胞毒性和活化的CD4+ T细胞、耗竭性和组织驻留记忆CD8+ T细胞、巨噬细胞、生发中心样B细胞、组织驻留和适应性NK细胞,以及调节性DCs,这些细胞存在于肿瘤中但在血液中缺失或不存在。我们的发现表明BC UDCs可能是TME的替代指标,并可作为治疗性生物标志物。
展开英文摘要原文
Due to bladder tumors' contact with urine, urine-derived cells (UDCs) may serve as a surrogate for monitoring the tumor microenvironment (TME) in bladder cancer (BC). However, the composition of UDCs and the extent to which they mirror the tumor remain poorly characterized. We generated the first single-cell RNA-sequencing of BC patient UDCs with matched tumor and peripheral blood mononuclear cells (PBMC). BC urine was more cellular than healthy donor (HD) urine, containing multiple immune populations including myeloid cells, CD4+ and CD8+ T cells, natural killer (NK) cells, B cells, and dendritic cells (DCs) in addition to tumor and stromal cells. Immune UDCs were transcriptionally more similar to tumor than blood. UDCs encompassed cytotoxic and activated CD4+ T cells, exhausted and tissue-resident memory CD8+ T cells, macrophages, germinal-center-like B cells, tissue-resident and adaptive NK cells, and regulatory DCs found in tumor but lacking or absent in blood. Our findings suggest BC UDCs may be surrogates for the TME and serve as therapeutic biomarkers.
论文信息
- 作者
- Tran MA、Youssef D、Shroff S、Chowhan D、Beaumont KG、Sebra R、Mehrazin R、Wiklund P
- 单位
- Division of Hematology and Medical Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.United States
- 文献类型
- 美国 NIH 资助研究
- 期刊
- The Journal of experimental medicine2024 Aug 5