Single-cell transcriptomic landscape reveals tumor specific innate lymphoid cells associated with colorectal cancer progression

Qi, Jingjing; Crinier, Adeline; Bertrand, Éric; Ye, Youqiong; Wang, Zhengting; Zhang, Tianyu; Batista, Luciana; Liu, Hongzhi; Hong, Liwen; Wu, Ningbo; Zhang, Mingnan; Chen, Lei; Liu, Yingbin; Shen, Lei; Narni-Mancinelli, Émilie; Vivier, Éric; Su, Bing

doi:10.1016/j.xcrm.2021.100353

Cited by 64 publications

(64 citation statements)

References 76 publications

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“…Similarly, activated DCs accumulate in the colon of UC patients [ 35 ] and their suppression by cancer cells has been hypothesized as a mechanism to avoid immune surveillance [ 36 ]. Notably, an increased abundance of activated DCs in invasive tumors, along with lymph node invasion, was observed [ 37 ].…”

Section: Discussionmentioning

confidence: 99%

Cell Type-Specific Induction of Inflammation-Associated Genes in Crohn’s Disease and Colorectal Cancer

Saul

Barros

Wixom

et al. 2022

IJMS

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Based on the rapid increase in incidence of inflammatory bowel disease (IBD), the identification of susceptibility genes and cell populations contributing to this condition is essential. Previous studies suggested multiple genes associated with the susceptibility of IBD; however, due to the analysis of whole-tissue samples, the contribution of individual cell populations remains widely unresolved. Single-cell RNA sequencing (scRNA-seq) provides the opportunity to identify underlying cellular populations. We determined the enrichment of Crohn’s disease (CD)-induced genes in a publicly available Crohn’s disease scRNA-seq dataset and detected the strongest induction of these genes in innate lymphoid cells (ILC1), highly activated T cells and dendritic cells, pericytes and activated fibroblasts, as well as epithelial cells. Notably, these genes were highly enriched in IBD-associated neoplasia, as well as sporadic colorectal cancer (CRC). Indeed, the same six cell populations displayed an upregulation of CD-induced genes in a CRC scRNA-seq dataset. Finally, after integrating and harmonizing the CD and CRC scRNA-seq data, we demonstrated that these six cell types display a gradual increase in gene expression levels from a healthy state to an inflammatory and tumorous state. Together, we identified cell populations that specifically upregulate CD-induced genes in CD and CRC patients and could, therefore, contribute to inflammation-associated tumor development.

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Section: Discussionmentioning

confidence: 99%

Cell Type-Specific Induction of Inflammation-Associated Genes in Crohn’s Disease and Colorectal Cancer

Saul

Barros

Wixom

et al. 2022

IJMS

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“…Previous studies have shown a role for ILC2s in both tumour promotion and tumour rejection, which have been comprehensively summarized elsewhere 57 . However, over the past 2 years, considerable progress has been made in the understanding of how specific populations of ILC2s contribute to immunosurveillance in different types of cancer 58 – 62 (Fig. 2 ).…”

Section: Ilc2s In Cancermentioning

confidence: 99%

Heterogeneity of type 2 innate lymphoid cells

Spits

Mjösberg

2022

Nat Rev Immunol

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More than a decade ago, type 2 innate lymphoid cells (ILC2s) were discovered to be members of a family of innate immune cells consisting of five subsets that form a first line of defence against infections before the recruitment of adaptive immune cells. Initially, ILC2s were implicated in the early immune response to parasitic infections, but it is now clear that ILC2s are highly diverse and have crucial roles in the regulation of tissue homeostasis and repair. ILC2s can also regulate the functions of other type 2 immune cells, including T helper 2 cells, type 2 macrophages and eosinophils. Dysregulation of ILC2s contributes to type 2-mediated pathology in a wide variety of diseases, potentially making ILC2s attractive targets for therapeutic interventions. In this Review, we focus on the spectrum of ILC2 phenotypes that have been described across different tissues and disease states with an emphasis on human ILC2s. We discuss recent insights in ILC2 biology and suggest how this knowledge might be used for novel disease treatments and improved human health.

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“…In contrast to the control tissues, ILCs from CRC patients were found to contain two additional subsets: a CRC tissue-specific ILC1-like subset and an ILC2 subset, the only two clusters that differ from the normal gut. Moreover, the expression of the SLAMF1 (signaling lymphocytic activation molecule family member 1) gene was upregulated in intratumoral ILCs, but only weakly expressed in their healthy counterparts, suggesting that SLAMF1 expression can be a predictive biomarker in CRC [203]. Finally, CRC severity was associated with a large number of ILC1s and an abnormal lower level of ILC3s in the intestine than at steady state [204].…”

Section: A Scrna-seq Gaze Of Helper-like Ilcsmentioning

confidence: 98%

“…ILCs are involved in cancer immunity and can contribute to tumor-associated inflammation. Their role appears to be TME-dependent [203]. For example, the scRNA-seq profile of intratumoral ILCs has been studied during CRC progression in mouse models [138].…”

Section: A Scrna-seq Gaze Of Helper-like Ilcsmentioning

confidence: 99%

“…Many studies have characterized ILC2s in mouse lungs [203,[210][211][212]: recent research [206] analyzed both adult and neonatal lungs and found two separated clusters of ILC2s defined by different gene signatures, one expressing conventional ILC2 genes such as Il1rl1 and Tnfrsf18 and the other expressing Cd7, Runx3, Tcf7 and Il18r1, but not Il1rl1 and Tnfrsf18.…”

Section: A Scrna-seq Gaze Of Helper-like Ilcsmentioning

confidence: 99%

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The Dual Role of Innate Lymphoid and Natural Killer Cells in Cancer. from Phenotype to Single-Cell Transcriptomics, Functions and Clinical Uses

Roma

Carpen

Raveane

2021

Cancers

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The role of innate lymphoid cells (ILCs), including natural killer (NK) cells, is pivotal in inflammatory modulation and cancer. Natural killer cell activity and count have been demonstrated to be regulated by the expression of activating and inhibitory receptors together with and as a consequence of different stimuli. The great majority of NK cell populations have an anti-tumor activity due to their cytotoxicity, and for this reason have been used for cellular therapies in cancer patients. On the other hand, the recently classified helper ILCs are fundamentally involved in inflammation and they can be either helpful or harmful in cancer development and progression. Tissue niche seems to play an important role in modulating ILC function and conversion, as observed at the transcriptional level. In the past, these cell populations have been classified by the presence of specific cellular receptor markers; more recently, due to the advent of single-cell RNA sequencing (scRNA-seq), it has been possible to also explore them at the transcriptomic level. In this article we review studies on ILC (and NK cell) classification, function and their involvement in cancer. We also summarize the potential application of NK cells in cancer therapy and give an overview of the most recent studies involving ILCs and NKs at scRNA-seq, focusing on cancer. Finally, we provide a resource for those who wish to start single-cell transcriptomic analysis on the context of these innate lymphoid cell populations.

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Single-cell transcriptomic landscape reveals tumor specific innate lymphoid cells associated with colorectal cancer progression

Cited by 64 publications

References 76 publications

Cell Type-Specific Induction of Inflammation-Associated Genes in Crohn’s Disease and Colorectal Cancer

Cell Type-Specific Induction of Inflammation-Associated Genes in Crohn’s Disease and Colorectal Cancer

Heterogeneity of type 2 innate lymphoid cells

The Dual Role of Innate Lymphoid and Natural Killer Cells in Cancer. from Phenotype to Single-Cell Transcriptomics, Functions and Clinical Uses

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