Single-Cell Analyses Inform Mechanisms of Myeloid-Targeted Therapies in Colon Cancer

Zhang, Lei; Li, Ziyi; Skrzypczynska, Katarzyna M.; Qiao, Fang; Zhang, Wei; O’Brien, Sarah; He, Yong; Wang, Lynn; Zhang, Qiming; Kim, AeRyon; Gao, Ranran; Orf, Jessica; Wang, Tao; Sawant, Deepali V.; Kang, Jiajinlong; Bhatt, Dev; Lu, Daniel; Li, Chi-Ming; Rapaport, Aaron S.; Perez, Kristy C.; Ye, Yingjiang; Wang, Shan; Hu, Xueda; Ren, Xianwen; Ouyang, Wenjun; Shen, Zhanlong; Egen, Jackson G.; Zhang, Zemin; Yu, Xin

doi:10.1016/j.cell.2020.03.048

Cited by 788 publications

(752 citation statements)

References 87 publications

Supporting

Mentioning

682

Contrasting

Order By: Relevance

“…It has been reported that LAYN and CCR8 are highly expressed in tumor-infiltrating Treg cells from colon cancer, non-small cell lung cancer, and liver cancer (6,33). We observed the consistently high expression of LAYN and CCR8 in Treg cells from four independent datasets (LIHC_GSE98638, NSCLC_GSE99254, COAD_GSE108989, and COAD_GSE146771_Smartseq2) (6,7,23,34), suggesting the tumor homogeneity in terms of cell phenotype signatures ( Figure 3D, Supplementary Figure S4). Besides the Treg cells, LAYN is also expressed in a subset of exhausted CD8T cells ( Figure 3D, Supplementary Figure S4).…”

Section: Multiple-dataset Comparisonsupporting

confidence: 52%

TISCH: a comprehensive web resource enabling interactive single-cell transcriptome visualization of tumor microenvironment

Sun

Wang

Han

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

Cancer immunotherapy targeting co-inhibitory pathways by checkpoint blockade shows remarkable efficacy in a variety of cancer types. However, only a minority of patients respond to treatment due to the stochastic heterogeneity of tumor microenvironment (TME). Recent advances in single-cell RNA-seq technologies enabled comprehensive characterization of the immune system heterogeneity in tumors, but also posed computational challenges on how to integrate and utilize the massive published datasets to inform immunotherapy. Here, we present Tumor Immune Single Cell Hub (TISCH, http://tisch.comp-genomics.org), a large-scale curated database that integrates single-cell transcriptomic profiles of nearly two million cells from 76 high-quality tumor datasets across 28 cancer types. All the data were uniformly processed with a standardized workflow, including quality control, batch effect removal, malignant cell classification, cell clustering, cell-type annotation, differential expression analysis, and functional enrichment analysis. TISCH provides interactive gene expression visualization across multiple datasets at the single-cell level or cluster level, allowing systematic comparison between different cell-types, patients, tissue origins, treatment and response groups, and even different cancer-types. In summary, TISCH provides a user-friendly interface for systematically visualizing, searching, and downloading gene expression atlas in the TME from multiple cancer types, enabling fast, flexible and comprehensive exploration of the TME.

show abstract

Section: Multiple-dataset Comparisonsupporting

confidence: 52%

TISCH: a comprehensive web resource enabling interactive single-cell transcriptome visualization of tumor microenvironment

Sun

Wang

Han

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…Specifically, TAMdirected therapies, such as anti-CSF1R antibodies, could be employed to selectively target transcriptionalsubtype-associated populations. 42,[53][54][55] However, while basal tumors associate with a potentially sensitive CSF1R-expressing population (C1QC+ TAM), classical tumors harbor TAMs that are resistant to such therapies (SPP1+ TAM). 42 Thus, just as we consider combinations to target malignant states, the TME will also likely require tailored combination therapies.…”

Section: Discussionmentioning

confidence: 99%

“…42,[53][54][55] However, while basal tumors associate with a potentially sensitive CSF1R-expressing population (C1QC+ TAM), classical tumors harbor TAMs that are resistant to such therapies (SPP1+ TAM). 42 Thus, just as we consider combinations to target malignant states, the TME will also likely require tailored combination therapies. These findings provide rationale for future clinical trials to employ highresolution phenotyping of malignant and non-malignant cells to stratify patients and track tumor evolution in response to therapy.…”

Section: Discussionmentioning

confidence: 99%

“…Relatively little is known about the structure and composition of the metastatic microenvironment in PDAC, and, more specifically, about how non-malignant heterogeneity associates with the basal to classical continuum. To 42,43 The first two PCs readily identified 3 TAM subsets: "monocyte-like" FCN1+, C1QC+, and SPP1+ macrophages (Extended Data Figure 6h). FCN1+ "monocyte-like" cells expressed high levels of IL1B and CCR2 and shared some features with CD14+ blood monocytes (CD300E, S100A8).…”

Section: Transcriptional Subtypes Associate With Distinct Immune Micrmentioning

confidence: 99%

“…FCN1+ "monocyte-like" cells expressed high levels of IL1B and CCR2 and shared some features with CD14+ blood monocytes (CD300E, S100A8). 42 We next determined whether the 18 non-malignant cell types/states were represented evenly across the malignant basal-to-classical transcriptional continuum described in 3g). In addition to demonstrating that classical tumors are relatively more immune infiltrated, this analysis also identifies distinct microenvironmental phenotypes that co-vary with each PDAC transcriptional subtype and suggests opportunities to direct microenvironmental therapies in a subtype-specific manner.…”

Section: Transcriptional Subtypes Associate With Distinct Immune Micrmentioning

confidence: 99%

See 2 more Smart Citations

The tumor microenvironment drives transcriptional phenotypes and their plasticity in metastatic pancreatic cancer

Raghavan

Winter

Navia

et al. 2020

Preprint

View full text Add to dashboard Cite

In pancreatic ductal adenocarcinoma (PDAC), the basal-like and classical transcriptional subtypes are associated with differential chemotherapy sensitivity and patient survival. These phenotypes have been defined using bulk transcriptional profiling, which can mask underlying cellular heterogeneity and the biologic mechanisms that distinguish these subtypes. Furthermore, few studies have interrogated metastases, which are the cause of mortality in most patients with this highly lethal disease. Using single-cell RNA-sequencing of metastatic needle biopsies and matched organoid models, we demonstrate intra-tumoral subtype heterogeneity at the single-cell level and define a continuum for the basal-like and classical phenotypes that includes hybrid cells that co-express features of both states. Basal-like tumors show enrichment of mesenchymal and stem-like programs, and demonstrate immune exclusion and tumor cell crosstalk with specific macrophage subsets. Conversely, classical tumors harbor greater immune infiltration and a relatively pro-angiogenic microenvironment. Matched organoid models exhibit a strong bias against the growth of basal-like cells in standard organoid media, but modification of culture conditions can rescue the basal-like phenotype. This study reframes the transcriptional taxonomy of PDAC, demonstrates how divergent transcriptional subtypes associate with unique tumor microenvironments, and highlights the importance of evaluating both genotype and transcriptional phenotype to establish high-fidelity patient-derived cancer models.

show abstract

Suppressive Myeloid Cells Shape the Tumor Immune Microenvironment

Xiong

Wang

2021

Advanced Biology

View full text Add to dashboard Cite

Cancer is the outcome of the conflict between the host immune system and cancer cells. The crosstalk between immune cells and tumor cells within the tumor microenvironment (TME) influences tumor progression and metastasis. Many studies have clarified the cellular and molecular events that can induce cancer cells to escape immune surveillance, including those involving tumor‐induced myeloid cell‐mediated immunosuppression. Emerging evidence indicates that tumor‐infiltrating myeloid cells (TIMs) accelerate tumor growth and induce angiogenesis, metastasis, and therapy resistance once converted into potent immunosuppressive cells. Here, how tumor infiltrating myeloid cells participate in tumor immune evasion and the prospects of these cells in cancer immunotherapy are discussed.

show abstract

Single-Cell Analyses Inform Mechanisms of Myeloid-Targeted Therapies in Colon Cancer

Cited by 788 publications

References 87 publications

TISCH: a comprehensive web resource enabling interactive single-cell transcriptome visualization of tumor microenvironment

TISCH: a comprehensive web resource enabling interactive single-cell transcriptome visualization of tumor microenvironment

The tumor microenvironment drives transcriptional phenotypes and their plasticity in metastatic pancreatic cancer

Suppressive Myeloid Cells Shape the Tumor Immune Microenvironment

Contact Info

Product

Resources

About