Integrated analysis of single-cell RNA-seq and bulk RNA-seq unravels tumour heterogeneity plus M2-like tumour-associated macrophage infiltration and aggressiveness in TNBC

Bao, Xuanwen; Shi, Run; Zhao, Tianyu; Wang, Yanfang; Anastasov, Nataša; Rosemann, Michael; Fang, Weijia

doi:10.1007/s00262-020-02669-7

Cited by 88 publications

(41 citation statements)

References 36 publications

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“…As a typically pro-tumorigenic cell, M2 macrophage plays an immunosuppressive role in the TME by inhibiting the activation of M1 macrophage and secreting IL-10 and TGF-β [30]. Current evidence supports the negative prognostic role of M2 macrophages in breast cancer [31]. Tumor endothelial cells may provide activation signals or secrete biglycan to stimulate cancer cell metastasis.…”

Section: Discussionmentioning

confidence: 97%

A Risk Scoring System Based on Tumor Microenvironment Cells to Predict Prognosis and Immune Activity in Triple-Negative Breast Cancer

Yang

et al. 2021

Preprint

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The tumor microenvironment (TME) interacting with the malignant cells plays a vital role in cancer development. Herein, we aim to establish and verify a scoring system based on the characteristics of TME cells for prognosis prediction and personalized treatment guidance in patients with triple-negative breast cancer (TNBC). 158 TNBC samples from The Cancer Genome Atlas (TCGA) were included as the training cohort, and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) (N = 297), as well as GSE58812 (N = 107), were included as the validation cohort. The enrichment scores of 64 immune and stromal cells were estimated by the xCell algorithm. In the training cohort, cells with prognostic significance were found out using univariate Cox regression analysis and further applied to the random survival forest (RSF) model. Basing on the scores of M2 macrophages, CD8+ T cells, and CD4+ memory T cells, a risk scoring system was constructed, which divided TNBC patients into 4 phenotypes (M2low, M2highCD8+ThighCD4+Thigh, M2highCD8+ThighCD4+Tlow, and M2highCD8+Tlow) and 2 groups. The low-risk group had superior survival outcomes than the high-risk one, which was further confirmed in the validation cohort. Moreover, in the low-risk group, immune-related pathways were significantly enriched, and a higher level of antitumoral immune cells and immune checkpoint molecules, including PD-L1, PD-1, and CTLA-4, could be observed. Additionally, consistent results were achieved in the SYSUCC cohort when the scoring system was applied. In summary, this novel scoring system might predict the survival and immune activity of patients and might serve as a potential index for immunotherapy.

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Section: Discussionmentioning

confidence: 97%

A Risk Scoring System Based on Tumor Microenvironment Cells to Predict Prognosis and Immune Activity in Triple-Negative Breast Cancer

Yang

et al. 2021

Preprint

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“…Although the number of profiled cells was low and the sequencing depth was limited, this work demonstrated the feasibility of a comprehensive characterization of the heterogeneous immunological microenvironment of breast cancer samples by large-scale single-cell gene expression profiling protocol. Recently, Bao et al (14) also described the molecular characteristics of M2-like TAM in the TME of breast cancer and identified the association of the immune landscape with clinical outcomes in TNBC by using an integrative analysis approach of combined single-cell and bulk tissue transcriptome profiling.…”

Section: Characterizing Immune Cell Heterogeneitymentioning

confidence: 99%

Single-Cell Profiling to Explore Immunological Heterogeneity of Tumor Microenvironment in Breast Cancer

et al. 2021

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Immune infiltrates in the tumor microenvironment (TME) of breast cancer (BRCA) have been shown to play a critical role in tumorigenesis, progression, invasion, and therapy resistance, and thereby will affect the clinical outcomes of BRCA patients. However, a wide range of intratumoral heterogeneity shaped by the tumor cells and immune cells in the surrounding microenvironment is a major obstacle in understanding and treating BRCA. Recent progress in single-cell technologies such as single-cell RNA sequencing (scRNA-seq), mass cytometry, and digital spatial profiling has enabled the detailed characterization of intratumoral immune cells and vastly improved our understanding of less-defined cell subsets in the tumor immune environment. By measuring transcriptomes or proteomics at the single-cell level, it provides an unprecedented view of the cellular architecture consist of phenotypical and functional diversities of tumor-infiltrating immune cells. In this review, we focus on landmark studies of single-cell profiling of immunological heterogeneity in the TME, and discuss its clinical applications, translational outlook, and limitations in breast cancer studies.

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“…Myeloid cells have been reported to be associated with ICB [28]. In the TCGA LUAD cohort, we introduced a tumor immune dysfunction and exclusion (TIDE) algorithm to explore the relationship between the MSC subtype and ICB response [29].…”

Section: Msc Subtype Associated With Immunotherapy Responsementioning

confidence: 99%

A fine-grained cell type deconvolution of bulk transcriptome from single-cell RNA-seq data reveals myeloid cells heterogeneity in lung adenocarcinomas

Wu¹,

Qin²,

Zhao³

et al. 2021

Preprint

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Background Tumor infiltrating myeloid cells (TIM) constitute a vital element of the tumor microenvironment. The cell-type heterogeneity of TIM has yet to be fully investigated. Methods We used a time saving approach to generate a single-cell reference matrix, allowing quantification of cell-type proportions and cell-type-specific gene abundances in bulk RNA-seq data. Results Two distinct clusters, MSC1 and MSC2 (MSC subtype) were newly identified in lung adenocarcinoma (LUAD) patients, both significantly associated with overall survival and immune blockade therapy responses. Twenty myeloid cell types were detected. Thirteen of these had distinct enrichment patterns between MSC1 and MSC2. LAMP3 + dendritic cells, being a mature and transportable subtype of dendritic cell which may migrate to lymph nodes, were noted as associated with non-responsiveness to immunotargeted therapy. High infiltration level of IFIT3 + neutrophils was strongly related to the response to immune targeted therapy and was seen to activate CD8 + T cells, partly through inflammasome activation. The infiltration levels of TIMP1 + macrophages and S100A8 + neutrophils were both significantly associated with poor prognosis. TIMP1 + macrophages were noted to recruit S100A8 + neutrophils via the CXCL5-CXCR2 axes and promote LUAD progression. Conclusion Altogether, we performed virtual micro-dissection of the bulk transcriptome at single-cell resolution and provided a promising TIM infiltration landscape that may shed new light on the development of immune therapy.

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Integrated analysis of single-cell RNA-seq and bulk RNA-seq unravels tumour heterogeneity plus M2-like tumour-associated macrophage infiltration and aggressiveness in TNBC

Cited by 88 publications

References 36 publications

A Risk Scoring System Based on Tumor Microenvironment Cells to Predict Prognosis and Immune Activity in Triple-Negative Breast Cancer

A Risk Scoring System Based on Tumor Microenvironment Cells to Predict Prognosis and Immune Activity in Triple-Negative Breast Cancer

Single-Cell Profiling to Explore Immunological Heterogeneity of Tumor Microenvironment in Breast Cancer

A fine-grained cell type deconvolution of bulk transcriptome from single-cell RNA-seq data reveals myeloid cells heterogeneity in lung adenocarcinomas

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