Computational modeling of malignant ascites reveals CCL5-SDC4 interaction in the immune microenvironment of ovarian cancer.
Computational modeling of malignant ascites reveals CCL5-SDC4 interaction in the immune microenvironment of ovarian cancer.
复制标题
DOI：
10.1002/mc.23289
复制
发表时间：
2021-05
影响因子：
4.6
通讯作者：
Song YS
中科院分区：
文献类型：
--
作者：
Kim S;Han Y;Kim SI;Lee J;Jo H;Wang W;Cho U;Park WY;Rando TA;Dhanasekaran DN;Song YS
腹腔积液常见于晚期卵巢癌患者，这为癌症进展创造了一个专门的肿瘤微环境。使用来自5名卵巢癌患者的腹水细胞的单细胞RNA测序（scRNA-seq），我们鉴定了7种细胞类型，包括异质性巨噬细胞和卵巢癌细胞。我们通过MacSpectrum分析解决了巨噬细胞的不同极化状态，并观察到与其功能相关的途径的亚型特异性富集。免疫细胞和癌细胞之间的通信是通过使用NicheNet的推定配体-受体对分析来预测的。我们发现CCL 5是一种趋化配体，富含免疫细胞（T细胞和NK细胞），并可能通过SDC 4介导卵巢癌细胞在腹水中的存活。此外，SDC 4表达与卵巢癌患者的总体生存率相关。我们的研究强调了T细胞和NK细胞在卵巢癌患者长期生存中的潜在作用，表明SDC 4是卵巢癌患者的潜在预后标志物。
Fluid accumulation in the abdominal cavity is commonly found in advanced-stage ovarian cancer patients, which creates a specialized tumor microenvironment for cancer progression. Using single-cell RNA sequencing (scRNA-seq) of ascites cells from 5 patients with ovarian cancer, we identified 7 cell types, including heterogeneous macrophages and ovarian cancer cells. We resolved a distinct polarization state of macrophages by MacSpectrum analysis and observed subtype-specific enrichment of pathways associated with their functions. The communication between immune and cancer cells was predicted through a putative ligand-receptor pair analysis using NicheNet. We found that CCL5, a chemotactic ligand, is enriched in immune cells (T cells and NK cells) and mediates ovarian cancer cell survival in the ascites, possibly through SDC4. Moreover, SDC4 expression correlated with poor overall survival in ovarian cancer patients. Our study highlights the potential role of T cells and NK cells in long-term survival in patients with ovarian cancer, indicating SDC4 as a potential prognostic marker in ovarian cancer patients.
登录
查看更多内容
影响因子：
5.8
作者：
Liberzon, Arthur;Subramanian, Aravind;Mesirov, Jill P.
通讯作者：
Mesirov, Jill P.
影响因子：
7.9
作者：
Kim S;Han Y;Kim SI;Kim HS;Kim SJ;Song YS
通讯作者：
Song YS
影响因子：
5.7
作者：
Kim S;Kim B;Song YS
通讯作者：
Song YS
影响因子：
3.6
作者：
Dufresne, Mathieu;Dumas, Genevieve;Reyes-Moreno, Carlos
通讯作者：
Reyes-Moreno, Carlos
影响因子：
4.6
作者：
Maccio, Antonio;Gramignano, Giulia;Madeddu, Clelia
通讯作者：
Madeddu, Clelia