TAMI-32. CORRELATION BETWEEN RADIOSENSITIVITY INDEX AND M2 MACROPHAGE PROPORTION IN TUMOR MICROENVIRONMENT OF GLIOBLASTOMA

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi204-vi205
Author(s):  
Bum-Sup Jang ◽  
In Ah Kim
Keyword(s):  
Overall Survival ◽  
Tumor Microenvironment ◽  
Single Cell ◽  
Rna Sequencing ◽  
The Cancer Genome Atlas ◽  
M2 Macrophage ◽  
M2 Macrophages ◽  
M1 Macrophage ◽  
Single Cell Rna Sequencing ◽  
Genome Atlas

Abstract BACKGROUND Tumor-associated macrophages (TAMs) Macrophage are predominant in glioblastoma tumor microenvironment (TME), supporting for neoplastic cell expansion and invasion. We investigated the relationship between radiosensitivity of glioblastoma and M1/M2 macrophage profiles in bulk and single cell RNA sequencing datasets. METHODS We used radiosensitivity index (RSI) gene signature and estimated RSI score based on the ranking of genes by expression level. Two large glioma datasets – The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) – were employed to identify whether RSI is clinically predictive of overall survival following radiation therapy. To analyze the association between M1/M2 macrophages and RSI within spatial context, the Ivy Glioblastoma Atlas Project dataset was investigated and single cell RNA sequencing dataset (GSE84465) was analyzed as well. Macrophages were profiled using a deconvolution algorithm, CIBERSORTx. RESULTS The RSI-high group having radioresistant tumors showed worse overall survival than the RSI-low group in both the TCGA (HR=1.87, 95% CI=1.06-3.29, P=0.031) and the CGGA (HR=1.61, 95% CI=1.04-2.50, P=0.031) glioblastoma population. In the Ivy Glioblastoma Atlas Project dataset, radiosensitive tumor having lower RSI was significantly more found in more vascular region including hyperplastic and microvascular region (coefficient=-0.07, P=0.001), meanwhile, radioresistant tumor was significantly clustered in necrotic region including perinecrotic and pseudopalisading regions (coefficient=0.07, P< 0.001). The proportion of M1/M2 macrophage and RSI score showed an inverse relationship (coefficient=-0.23, P=0.015), indicating that radioresistant glioblastomas are related with TME having more M2 than M1 macrophage. In single cell RNA sequencing dataset composed of immune and tumor cells collected from four patients, mean RSI of neoplastic cells was positively correlated with high proportion of M2 macrophages. CONCLUSION RSI can predict radiation response in terms of overall survival in glioblastoma patients. High proportion of M2 macrophage may play an important role in TME of radioresistant glioblastoma.

scholarly journals Single-cell RNA sequencing reveals distinct tumor microenvironmental patterns in lung adenocarcinoma

Oncogene ◽  
2021 ◽  
Author(s):  
Philip Bischoff ◽  
Alexandra Trinks ◽  
Benedikt Obermayer ◽  
Jan Patrick Pett ◽  
Jennifer Wiederspahn ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Tumor Microenvironment ◽  
Lung Adenocarcinoma ◽  
Single Cell ◽  
Rna Sequencing ◽  
Histological Grade ◽  
Cell Populations ◽  
Marker Genes ◽  
Single Cell Rna Sequencing

AbstractRecent developments in immuno-oncology demonstrate that not only cancer cells, but also the tumor microenvironment can guide precision medicine. A comprehensive and in-depth characterization of the tumor microenvironment is challenging since its cell populations are diverse and can be important even if scarce. To identify clinically relevant microenvironmental and cancer features, we applied single-cell RNA sequencing to ten human lung adenocarcinomas and ten normal control tissues. Our analyses revealed heterogeneous carcinoma cell transcriptomes reflecting histological grade and oncogenic pathway activities, and two distinct microenvironmental patterns. The immune-activated CP²E microenvironment was composed of cancer-associated myofibroblasts, proinflammatory monocyte-derived macrophages, plasmacytoid dendritic cells and exhausted CD8+ T cells, and was prognostically unfavorable. In contrast, the inert N³MC microenvironment was characterized by normal-like myofibroblasts, non-inflammatory monocyte-derived macrophages, NK cells, myeloid dendritic cells and conventional T cells, and was associated with a favorable prognosis. Microenvironmental marker genes and signatures identified in single-cell profiles had progonostic value in bulk tumor profiles. In summary, single-cell RNA profiling of lung adenocarcinoma provides additional prognostic information based on the microenvironment, and may help to predict therapy response and to reveal possible target cell populations for future therapeutic approaches.

scholarly journals Single-Cell RNA Sequencing Reveals Multiple Pathways and the Tumor Microenvironment Could Lead to Chemotherapy Resistance in Cervical Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Meijia Gu ◽  
Ti He ◽  
Yuncong Yuan ◽  
Suling Duan ◽  
Xin Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cervical Cancer ◽  
Tumor Microenvironment ◽  
Single Cell ◽  
Rna Sequencing ◽  
Cancer Biology ◽  
Chemotherapy Resistance ◽  
Cell Types ◽  
Functional Enrichment ◽  
Single Cell Rna Sequencing

BackgroundCervical cancer is one of the most common gynecological cancers worldwide. The tumor microenvironment significantly influences the therapeutic response and clinical outcome. However, the complex tumor microenvironment of cervical cancer and the molecular mechanisms underlying chemotherapy resistance are not well studied. This study aimed to comprehensively analyze cells from pretreated and chemoresistant cervical cancer tissues to generate a molecular census of cell populations.MethodsBiopsy tissues collected from patients with cervical squamous cell carcinoma, cervical adenocarcinoma, and chronic cervicitis were subjected to single-cell RNA sequencing using the 10× Genomics platform. Unsupervised clustering analysis of cells was performed to identify the main cell types, and important cell clusters were reclustered into subpopulations. Gene expression profiles and functional enrichment analysis were used to explore gene expression and functional differences between cell subpopulations in cervicitis and cervical cancer samples and between chemoresistant and chemosensitive samples.ResultsA total of 24,371 cells were clustered into nine separate cell types, including immune and non-immune cells. Differentially expressed genes between chemoresistant and chemosensitive patients enriched in the phosphoinositide 3-kinase (PI3K)/AKT pathway were involved in tumor development, progression, and apoptosis, which might lead to chemotherapy resistance.ConclusionsOur study provides a comprehensive overview of the cancer microenvironment landscape and characterizes its gene expression and functional difference in chemotherapy resistance. Consequently, our study deepens the insights into cervical cancer biology through the identification of gene markers for diagnosis, prognosis, and therapy.

scholarly journals Single-cell RNA sequencing reveals distinct tumor microenvironmental patterns in lung adenocarcinoma

2020 ◽  
Author(s):  
Philip Bischoff ◽  
Alexandra Trinks ◽  
Benedikt Obermayer ◽  
Jan Patrick Pett ◽  
Annika Lehmann ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Tumor Microenvironment ◽  
Single Cell ◽  
Rna Sequencing ◽  
Histological Grade ◽  
Myeloid Dendritic Cells ◽  
Oncogenic Pathways ◽  
Single Cell Rna Sequencing ◽  
Cell Gene Expression

Recent developments in immuno-oncology demonstrate that not only cancer cells, but also features of the tumor microenvironment guide precision medicine. Still, the relationship between tumor and microenvironment remains poorly understood. To overcome this limitation and identify clinically relevant microenvironmental and cancer features, we applied single-cell RNA sequencing to lung adenocarcinomas. While the highly heterogeneous carcinoma cell transcriptomes reflected histological grade and activity of relevant oncogenic pathways, our analysis revealed two distinct microenvironmental patterns. We identified a prognostically unfavorable group of tumors with a microenvironment composed of cancer-associated myofibroblasts, exhausted CD8+ T cells, proinflammatory monocyte-derived macrophages and plasmacytoid dendritic cells (CEP2 pattern) and a prognostically favorable group characterized by myeloid dendritic cells, anti-inflammatory monocyte-derived macrophages, normal-like myofibroblasts, NK cells and conventional T cells (MAN2C pattern). Our results show that single-cell gene expression profiling allows to identify patient subgroups based on the tumor microenvironment beyond cancer cell-centric profiling.

Landscape of Cell Heterogeneity and Evolutionary Trajectory in Ulcerative Colitis-associated Colon Cancer Revealed by Single-cell Rna Sequencing

2020 ◽  
Author(s):  
Quan Wang ◽  
Zhu Wang ◽  
Zhen Zhang ◽  
Wei Zhang ◽  
Mengmeng Zhang ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Colon Cancer ◽  
Single Cell ◽  
Rna Sequencing ◽  
Developmental Trajectory ◽  
The Cancer Genome Atlas ◽  
Cell Heterogeneity ◽  
Evolutionary Trajectory ◽  
Cell Clusters ◽  
Single Cell Rna Sequencing

Abstract Background: Patients with colitis-associated cancer (CAC), a particular kind of colorectal cancer that develops from inflammatory bowel diseases (IBDs), have an earlier morbidity and a poorer prognosis. However, in CAC, single cell transcriptome analysis of the microenvironment composition and characteristics has yet to be performed. To understand the intra-tumor heterogeneity in CAC and to reveal a potential evolutionary trajectory from ulcerative colitis (UC) to CAC at the single cell level. Methods: Fresh samples of tumor- and adjacent tissue, from a CAC patient with pT3N1M0, were examined by single cell RNA sequencing (scRNA-seq). Data from The Cancer Genome Atlas (TCGA) and The Human Protein Atlas were used to confirm the different expression levels in normal and tumor tissues and to determine their relationships with prognosis. Results: Ultimately, 4,777 single-cell transcriptomes (1220 genes per cell) were studied, which composed of 2,250 (47%) and 2,527(53%) originated from tumor- and non-malignant tissue, respectively. And we defined the composition of cancer-associated stromal cells and identified six cell clusters included myeloid, T and B cells, fibroblasts, endothelial and epithelial cells. Likewise, the notable pathways and transcription factors (TFs) involved of these cell clusters were analyzed and described. Moreover, we graphed the precise cellular composition and developmental trajectory from UC to UC-associated colon cancer, and predicted that CD74, CLCA1 and DPEP1 had a potential role in the disease progression. Conclusions: scRNA-seq technology could reveal intratumor cell heterogeneity in ulcerative colitis-associated colon cancer, and might provide a promising direction to seek the novel potential therapeutic targets in the evolution from IBD to CAC.

scholarly journals Abstract 124: Evaluating heterogeneity of tumor microenvironment using single cell RNA sequencing

2019 ◽  
Author(s):  
Untack Cho ◽  
Yong Sang Song ◽  
Woong-Yang Park ◽  
Hae-Ock Lee ◽  
Youngjin Han
Keyword(s):  
Tumor Microenvironment ◽  
Single Cell ◽  
Rna Sequencing ◽  
Single Cell Rna Sequencing

scholarly journals Single-cell RNA-sequencing analysis of estrogen- and endocrine-disrupting chemical-induced reorganization of mouse mammary gland

2019 ◽  
Vol 2 (1) ◽  
Author(s):  
Noriko Kanaya ◽  
Gregory Chang ◽  
Xiwei Wu ◽  
Kohei Saeki ◽  
Lauren Bernal ◽  
...  
Keyword(s):  
Mammary Gland ◽  
Epithelial Cells ◽  
Single Cell ◽  
Rna Sequencing ◽  
Mammary Tissue ◽  
M2 Macrophage ◽  
Sequencing Analysis ◽  
Endocrine Disrupting ◽  
Single Cell Rna Sequencing ◽  
Luminal Epithelial Cells

Abstract Menopause is a critical window of susceptibility for its sensitivity to endocrine disrupting chemicals due to the decline of endogenous estrogen. Using a surgical menopausal (ovariectomized) mouse model, we assessed how mammary tissue was affected by both 17β-estradiol (E2) and polybrominated diphenyl ethers (PBDEs). As flame retardants in household products, PBDEs are widely detected in human serum. During physiologically-relevant exposure to E2, PBDEs enhanced E2-mediated regrowth of mammary glands with terminal end bud-like structures. Analysis of mammary gland RNA revealed that PBDEs both augmented E2-facilitated gene expression and modulated immune regulation. Through single-cell RNA sequencing (scRNAseq) analysis, E2 was found to induce Pgr expression in both Esr1+ and Esr1− luminal epithelial cells and Ccl2 expression in Esr1+ fibroblasts. PBDEs promote the E2-AREG-EGFR-M2 macrophage pathway. Our findings support that E2 + PBDE increases the risk of developing breast cancer through the expansion of estrogen-responsive luminal epithelial cells and immune modulation.

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