Single‐cell analyses reveal suppressive tumor microenvironment of human colorectal cancer

Yan, Mei; Xiao, Weiwei; Hu, Hao; Lu, Guan-Ming; Chen, Lingdan; Sun, Zhun; Lü, Mengdie; Ma, Wenhui; Jiang, Ting; Gao, Yuanhong; Li, LiRen; Chen, Gong; Wang, Zifeng; Li, Hanjie; Wu, Duojiao; Zhou, Ping‐Hong; Leng, Qibin; Jia, Guangshuai

doi:10.1002/ctm2.422

Cited by 59 publications

(47 citation statements)

References 46 publications

(66 reference statements)

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“…Prior work has aimed to identify transcriptional and epigenetic signatures of macrophage states [52][53][54][55][56][57][58] . More recently, single-cell sequencing approaches have been leveraged for an unbiased data-driven characterization of macrophage states in various physiologic and pathologic contexts [59][60][61][62][63][64] . These studies rely on profiling the abundance of molecules using a snap-shot measurement to characterize macrophage states.…”

Section: Discussionmentioning

confidence: 99%

Stimulus-Response signaling dynamics characterize macrophage polarization states

Singh

Sen

Adelaja

et al. 2022

Preprint

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Macrophages show remarkable functional pleiotropy that is dependent on microenvironmental context. Prior studies have characterized how polarizing cytokines alter the transcriptomic and epigenetic landscape. Here we characterized the immune-threat appropriate responses of polarized macrophages by measuring the single-cell signaling dynamics of transcription factor NFκB. Leveraging a fluorescent protein reporter mouse, primary macrophages were polarized into 6 states and stimulated with 8 different stimuli resulting in a vast dataset. Linear Discriminant Analysis revealed how NFκB signaling codons compose the immune threat level of stimuli, placing polarization states along a linear continuum between the M1/M2 dichotomy. Machine learning classification revealed losses of stimulus distinguishability with polarization, which reflect a switch from sentinel to more canalized effector functions. However, the stimulus- response dynamics and discrimination patterns did not fit the M1/M2 continuum. Instead, our analysis suggests macrophage functional niches within a multi-dimensional polarization landscape.

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Section: Discussionmentioning

confidence: 99%

Stimulus-Response signaling dynamics characterize macrophage polarization states

Singh

Sen

Adelaja

et al. 2022

Preprint

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“…Mei et al. integrated scRNA‐seq with whole‐exome sequencing and transposase‐accessible chromatin assays using sequencing (scATAC‐seq) to illustrate molecular communications between cancer cells, between immune cells, and between cancer cells and immune cells 18 . The study focused on cancer cell tumour mutational burdens (TMB) with various transcriptomic profiles, epigenetic landscapes, and interactions with immune cells, although the mutation and transcriptomics were not measured in the exact same single cell.…”

Section: Figurementioning

confidence: 99%

“…Within the microenvironment where 2/7 had high TMB and 5/7 had low TMB, the number of Th1/Th17 cells with CXCL13 and the expression of lymphotactin 1 and 2 (XCL1 and XCL2) bound to chemokine XC receptor 1 and 2 (XCR1 and XCR2) in CD8 + CTL and TEX cells were increased in high TMB. 18 Patients with high TMB were more sensitive to the immune‐checkpoint blockade of PD‐1. However, it is still difficult to define transcriptomic profiles of single cells with high TMB because it is difficult to distinguish normal epithelia and cancer cells from the same microenvironment, to measure whole‐exome sequencing and scRNA‐seq simultaneously, and to uncover the direct association between mutation and regulatory network functions.…”

mentioning

confidence: 99%

“…In this particular study, scRNA‐seq was performed in 12 treatment‐naïve patients with colorectal cancer at stages I–IV, whole‐exome sequencing in seven patients, and scATAC‐seq in six patients. 18 Clinical studies on immune single‐cell profiles can also provide valuable information for understanding the effects of immune cells within systemic and local environments on disease severity, stage, and response to therapy. For example, 18 patients with breast cancer were enrolled and divided into four groups based on luminal A and B, HER‐2, and TNBC subtypes, into two groups on biopsies and surgical sections, on different sites of the tumour, or pre‐ and postoperation, as well as into three groups on pre, mid‐, and posttreatments with drugs.…”

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confidence: 99%

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Forward single‐cell sequencing into clinical application: Understanding of cancer microenvironment at single‐cell solution

Liu

Wang

2022

Clinical & Translational Med

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Single‐cell RNA sequencing (scRNA‐seq) is considered an important approach to understand the molecular mechanisms of cancer microenvironmental functions and has the potential for clinical and translational discovery and development. The recent concerns on the impact of scRNA‐seq for clinical practice are whether scRNA can be applied as a routine measurement of clinical biochemistry to assist in clinical decision‐making for diagnosis and therapy. Pushing single‐cell sequencing into clinical application is one of the important missions for clinical and translational medicine (CTM), although there still are a large number of challenges to be overcome. The present Editorial as one of serials aims at overviewing the history of scRNA‐seq publications in CTM, sharing the understanding and consideration of the cancer microenvironment at the single‐cell solution and emphasising the objective of translating scRNA‐seq into clinical application. The dynamic characteristics and patterns of single‐cell identity, regulatory networks, and intercellular communication play decisive roles in the properties of the microenvironment, malignancy and migrative capacity of cancer cells, and defensive capacity of immune cells. The microenvironmental single‐cell transcriptomic profiles and cell clusters defined by scRNA‐seq have great value for exploring the molecular mechanisms of diseases and predicting cell sensitivities to therapy and patient prognosis.

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“…Immune evasion is a critical hallmark of solid cancer development ( 9 ). The establishment of immune suppressive tumor microenvironment (TME) is a prerequisite for the initiation and progression of a majority of solid tumors, including CRC ( 10 , 11 ). The establishment of immunosuppressive environment involves a variety of cell types, such as tumor cells, immune cells, stromal cells.…”

Section: Introductionmentioning

confidence: 99%

High Expression of CSF-1R Predicts Poor Prognosis and CSF-1Rhigh Tumor-Associated Macrophages Inhibit Anti-Tumor Immunity in Colon Adenocarcinoma

Wang

Zhang

et al. 2022

Front. Oncol.

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BackgroundColony stimulating factor 1 receptor (CSF-1R) is a single channel III transmembrane receptor tyrosine kinase (RTK) and plays an important role in immune regulation and the development of various cancer types. The expression of CSF-1R in colon adenocarcinoma (COAD) and its prognostic value remain incompletely understood. Therefore, we aim to explore the prognostic value of CSF-1R in COAD and its relationship with tumor immunity.MethodsCSF-1R expression in a COAD cohort containing 103 patients was examined using immunohistochemistry (IHC). The relationship between CSF-1R expression and clinicopathological parameters and prognosis was evaluated. Dual immunofluorescence staining was conducted to determine the localization of CSF-1R in COAD tissues. Univariate and multivariate Cox regression analysis were performed to evaluate independent prognostic factors. Transcriptomic profiles of CSF-1Rhigh and CSF-1Rlow tumor-associated macrophages (TAMs) were investigated. Gene enrichment analysis was used to explore the signal pathways related to CSF-1R. In addition, the relationship between CSF-1R in tumor microenvironment (TME) and tumor immunity was also studied.ResultsIHC analysis showed that CSF-1R was overexpressed in COAD, and higher expression was associated with shorter overall survival (OS). Immunofluorescence staining showed that CSF-1R was co-localized with macrophage marker CD68. Univariate and multivariate Cox regression analysis showed that CSF-1R was an independent prognostic factor for COAD. The results of gene enrichment analysis showed that CSF-1R was involved in tumor immune response and regulation of TME. In addition, CSF-1R was significantly correlated with TME, immune cell infiltration, TMB, MSI, Neoantigen, and immune checkpoint molecules.ConclusionCSF-1R can serve as an independent prognostic factor of COAD and promising immunotherapeutic target of COAD.

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Single‐cell analyses reveal suppressive tumor microenvironment of human colorectal cancer

Cited by 59 publications

References 46 publications

Stimulus-Response signaling dynamics characterize macrophage polarization states

Stimulus-Response signaling dynamics characterize macrophage polarization states

Forward single‐cell sequencing into clinical application: Understanding of cancer microenvironment at single‐cell solution

High Expression of CSF-1R Predicts Poor Prognosis and CSF-1Rhigh Tumor-Associated Macrophages Inhibit Anti-Tumor Immunity in Colon Adenocarcinoma

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