Modulation of Immune Infiltration of Ovarian Cancer Tumor Microenvironment by Specific Subpopulations of Fibroblasts.
Modulation of Immune Infiltration of Ovarian Cancer Tumor Microenvironment by Specific Subpopulations of Fibroblasts.
复制标题
成纤维细胞特定亚群对卵巢癌肿瘤微环境免疫浸润的调节作用 。
DOI：
10.3390/cancers12113184
复制
发表时间：
2020-10-29
期刊：
影响因子：
5.2
通讯作者：
Mitra AK
中科院分区：
文献类型：
--
作者：
Wang J;Cheng FHC;Tedrow J;Chang W;Zhang C;Mitra AK
卵巢癌肿瘤微环境由卵巢癌细胞以及蛋白质和正常细胞环境组成，包括成纤维细胞、免疫细胞、内皮细胞、周细胞和脂肪细胞。非癌症成分在决定肿瘤的命运方面也发挥着重要作用，并表现出很多异质性。在这项研究中，我们使用反卷积算法从卵巢癌原发肿瘤、转移瘤和正常大网膜的大量 RNA-seq 数据中识别出四种不同的成纤维细胞亚群和多种免疫细胞类型。我们报告了决定肿瘤免疫微环境的特定成纤维细胞亚型的流行情况。我们的研究可能有助于提供一个模板，用于识别潜在的联合疗法，以增强卵巢癌免疫疗法的疗效。 Tumor immune infiltration plays a key role in the progression of solid tumors, including ovarian cancer, and immunotherapies are rapidly emerging as effective treatment modalities.然而，癌症相关成纤维细胞（CAF）是一种主要基质成分，在确定肿瘤免疫微环境和调节免疫疗法疗效中的作用仍知之甚少。我们对我们的和其他公开的卵巢癌数据集（GSE137237、GSE132289 和 GSE71340）进行了广泛的生物信息学分析，以确定肿瘤微环境（TME）内成纤维细胞亚型与肿瘤免疫浸润特征的相关性。我们确定了（1）卵巢癌中与卵巢癌 TME 和转移相关的 CAF 的四个功能模块，（2）原发性卵巢癌和网膜转移中表达胶原蛋白 1,3,5 的 CAF 的免疫抑制功能，以及（3）CAF 的功能模块与抗免疫反应基因一致的正相关性和与促免疫反应基因的负相关性。我们的研究在卵巢癌肿瘤微环境中确定了一种特定的成纤维细胞亚型，即成纤维细胞功能模块（FFM）2，它可以潜在地调节促进肿瘤的免疫微环境，这可能不利于卵巢癌免疫疗法的有效性。
The ovarian cancer tumor microenvironment is made up of ovarian cancer cells along with a milieu of proteins and normal cells, including fibroblasts, immune cells, endothelial cells, pericytes and adipocytes. The noncancer components also play an important role in determining the fate of the tumor and exhibit a lot of heterogeneity. In this study, we have used a deconvolution algorithm to identify four different fibroblast subpopulations and multiple immune cell types, from bulk RNA-seq data of ovarian cancer primary tumors, metastases and normal omentum. We report the prevalence of specific fibroblast subtypes that determine the tumor-immune microenvironment. Our study can potentially help provide a template for identification of potential combination therapies to enhance the efficacy of ovarian cancer immunotherapies. Tumor immune infiltration plays a key role in the progression of solid tumors, including ovarian cancer, and immunotherapies are rapidly emerging as effective treatment modalities. However, the role of cancer-associated fibroblasts (CAFs), a predominant stromal constituent, in determining the tumor-immune microenvironment and modulating efficacy of immunotherapies remains poorly understood. We have conducted an extensive bioinformatic analysis of our and other publicly available ovarian cancer datasets (GSE137237, GSE132289 and GSE71340), to determine the correlation of fibroblast subtypes within the tumor microenvironment (TME) with the characteristics of tumor-immune infiltration. We identified (1) four functional modules of CAFs in ovarian cancer that are associated with the TME and metastasis of ovarian cancer, (2) immune-suppressive function of the collagen 1,3,5-expressing CAFs in primary ovarian cancer and omental metastases, and (3) consistent positive correlations between the functional modules of CAFs with anti-immune response genes and negative correlation with pro-immune response genes. Our study identifies a specific fibroblast subtype, fibroblast functional module (FFM)2, in the ovarian cancer tumor microenvironment that can potentially modulate a tumor-promoting immune microenvironment, which may be detrimental toward the effectiveness of ovarian cancer immunotherapies.
登录
查看更多内容
DOI：
10.1158/1078-0432.ccr-08-1283
发表时间：
2009-02-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Beck AH;Espinosa I;Edris B;Li R;Montgomery K;Zhu S;Varma S;Marinelli RJ;van de Rijn M;West RB
通讯作者：
West RB
DOI：
10.1016/j.tem.2017.02.009
发表时间：
2017-06
期刊：
Trends in endocrinology and metabolism: TEM
影响因子：
--
作者：
Gabriely G;Wheeler MA;Takenaka MC;Quintana FJ
通讯作者：
Quintana FJ
影响因子：
8.8
作者：
Hart, Peter C.;Kenny, Hilary A.;Romero, Iris L.
通讯作者：
Romero, Iris L.
DOI：
10.1073/pnas.1320318110
发表时间：
2013-12-10
影响因子：
11.1
作者：
Feig, Christine;Jones, James O.;Fearon, Douglas T.
通讯作者：
Fearon, Douglas T.
影响因子：
4.3
作者：
DERIE, MA;SCHUMACHER, TNM;MIEDEMA, F
通讯作者：
MIEDEMA, F