Analysis of Gene Signatures of Tumor Microenvironment Yields Insight Into Mechanisms of Resistance to Immunotherapy

Wang, Ben; Liu, Mengmeng; Ran, Zhujie; Li, Xin; Li, Jie; Ou, Yunsheng

doi:10.3389/fbioe.2020.00348

Cited by 3 publications

(1 citation statement)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, the identification of disease states in individual pulmonary fibrosis derived cells led to the human pulmonary fibrosis atlas, serving as a groundwork for personalised therapies [12]. scRNA-seq was effectively adopted in cancer research, aiming to identify individualised treatment-targets and improve patient care [13][14][15]. Recently, the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) pandemic further boosted applications of scRNA-seq in lungs due to the need to understand cellular pathomechanisms underlying coronavirus disease 2019 (COVID- 19).…”

Section: Introductionmentioning

confidence: 99%

A pulmonologist's guide to perform and analyse cross-species single lung cell transcriptomics

et al. 2022

View full text Add to dashboard Cite

Single-cell ribonucleic acid sequencing is becoming widely employed to study biological processes at a novel resolution depth. The ability to analyse transcriptomes of multiple heterogeneous cell types in parallel is especially valuable for cell-focused lung research where a variety of resident and recruited cells are essential for maintaining organ functionality. We compared the single-cell transcriptomes from publicly available and unpublished datasets of the lungs in six different species: human (Homo sapiens), African green monkey (Chlorocebus sabaeus), pig (Sus domesticus), hamster (Mesocricetus auratus), rat (Rattus norvegicus) and mouse (Mus musculus) by employing RNA velocity and intercellular communication based on ligand–receptor co-expression, among other techniques. Specifically, we demonstrated a workflow for interspecies data integration, applied a single unified gene nomenclature, performed cell-specific clustering and identified marker genes for each species. Overall, integrative approaches combining newly sequenced as well as publicly available datasets could help identify species-specific transcriptomic signatures in both healthy and diseased lung tissue and select appropriate models for future respiratory research.

show abstract

Section: Introductionmentioning

confidence: 99%

A pulmonologist's guide to perform and analyse cross-species single lung cell transcriptomics

et al. 2022

View full text Add to dashboard Cite

show abstract

Single-cell RNA sequencing in cancer: Applications, advances, and emerging challenges

Sun

Ding

et al. 2021

Molecular Therapy - Oncolytics

View full text Add to dashboard Cite

Cancer has become one of the greatest threats to human health, and new technologies are urgently needed to further clarify the mechanisms of cancer so that better detection and treatment strategies can be developed. At present, extensive genomic analysis and testing of clinical specimens shape the insights into carcinoma. Nevertheless, carcinoma of humans is a complex ecosystem of cells, including carcinoma cells and immunityrelated and stroma-related subsets, with accurate characteristics obscured by extensive genome-related approaches. A growing body of research shows that sequencing of single-cell RNA (scRNA-seq) is emerging to be an effective way for dissecting human tumor tissue at single-cell resolution, presenting one prominent way for explaining carcinoma biology. This review summarizes the research progress of scRNA-seq in the field of tumors, focusing on the application of scRNA-seq in tumor circulating cells, tumor stem cells, tumor drug resistance, the tumor microenvironment, and so on, which provides a new perspective for tumor research.

show abstract

Lipid-Associated Macrophages Are Induced by Cancer-Associated Fibroblasts and Mediate Immune Suppression in Breast Cancer

et al. 2022

View full text Add to dashboard Cite

Tumor-associated macrophages (TAM) play a detrimental role in triple-negative breast cancer (TNBC). In-depth analysis of TAM characteristics and interactions with stromal cells, such as cancer-associated fibroblast (CAF), could provide important biological and therapeutic insights. Here we identify at the single-cell level a monocyte-derived-STAB1+TREM2high lipid-associated macrophage (LAM) subpopulation with immune suppressive capacities that is expanded in patients resistant to immune checkpoint blockade (ICB). Genetic depletion of this LAM subset in mice suppressed TNBC tumor growth. Flow cytometry and bulk-RNA sequencing data demonstrated that co-culture with TNBC-derived CAFs led to reprogramming of blood monocytes towards immune suppressive STAB1+TREM2high LAMs, which inhibit T cell activation and proliferation. Cell-to-cell interaction modeling and assays in vitro demonstrated the role of the inflammatory CXCL12-CXCR4 axis in CAF-myeloid cell crosstalk and recruitment of monocytes in tumor sites. Altogether, these data suggest an inflammation model whereby monocytes recruited to the tumor via the CAF-driven CXCL12-CXCR4 axis acquire pro-tumorigenic LAM capacities to support an immunosuppressive microenvironment.

show abstract

Analysis of Gene Signatures of Tumor Microenvironment Yields Insight Into Mechanisms of Resistance to Immunotherapy

Cited by 3 publications

References 51 publications

A pulmonologist's guide to perform and analyse cross-species single lung cell transcriptomics

A pulmonologist's guide to perform and analyse cross-species single lung cell transcriptomics

Single-cell RNA sequencing in cancer: Applications, advances, and emerging challenges

Lipid-Associated Macrophages Are Induced by Cancer-Associated Fibroblasts and Mediate Immune Suppression in Breast Cancer

Contact Info

Product

Resources

About