Single-Cell Transcriptomics in Cancer Immunobiology: The Future of Precision Oncology

Cancer is a heterogeneous and complex disease. Tumors are formed by cancer cells and a myriad of non-cancerous cell types that together with the extracellular matrix form the tumor microenvironment. These cancer-associated cells and components contribute to shape the progression of cancer and are de...

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Main Authors: Fatima Valdes-Mora, Kristina Handler, Andrew M. K. Law, Robert Salomon, Samantha R. Oakes, Christopher J. Ormandy, David Gallego-Ortega
Format: Article
Language:English
Published: Frontiers Media S.A. 2018-11-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fimmu.2018.02582/full
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author Fatima Valdes-Mora
Fatima Valdes-Mora
Kristina Handler
Andrew M. K. Law
Robert Salomon
Samantha R. Oakes
Samantha R. Oakes
Christopher J. Ormandy
Christopher J. Ormandy
David Gallego-Ortega
David Gallego-Ortega
author_facet Fatima Valdes-Mora
Fatima Valdes-Mora
Kristina Handler
Andrew M. K. Law
Robert Salomon
Samantha R. Oakes
Samantha R. Oakes
Christopher J. Ormandy
Christopher J. Ormandy
David Gallego-Ortega
David Gallego-Ortega
author_sort Fatima Valdes-Mora
collection DOAJ
description Cancer is a heterogeneous and complex disease. Tumors are formed by cancer cells and a myriad of non-cancerous cell types that together with the extracellular matrix form the tumor microenvironment. These cancer-associated cells and components contribute to shape the progression of cancer and are deeply involved in patient outcome. The immune system is an essential part of the tumor microenvironment, and induction of cancer immunotolerance is a necessary step involved in tumor formation and growth. Immune mechanisms are intimately associated with cancer progression, invasion, and metastasis; as well as to tumor dormancy and modulation of sensitivity to drug therapy. Transcriptome analyses have been extensively used to understand the heterogeneity of tumors, classifying tumors into molecular subtypes and establishing signatures that predict response to therapy and patient outcomes. However, the classification of the tumor cell diversity and specially the identification of rare populations has been limited in these transcriptomic analyses of bulk tumor cell populations. Massively-parallel single-cell RNAseq analysis has emerged as a powerful method to unravel heterogeneity and to study rare cell populations in cancer, through unsupervised sampling and modeling of transcriptional states in single cells. In this context, the study of the role of the immune system in cancer would benefit from single cell approaches, as it will enable the characterization and/or discovery of the cell types and pathways involved in cancer immunotolerance otherwise missed in bulk transcriptomic information. Thus, the analysis of gene expression patterns at single cell resolution holds the potential to provide key information to develop precise and personalized cancer treatment including immunotherapy. This review is focused on the latest single-cell RNAseq methodologies able to agnostically study thousands of tumor cells as well as targeted single-cell RNAseq to study rare populations within tumors. In particular, we will discuss methods to study the immune system in cancer. We will also discuss the current challenges to the study of cancer at the single cell level and the potential solutions to the current approaches.
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spelling doaj.art-27903686e0c942289f8c9dfe1b98c6692022-12-22T02:03:20ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-11-01910.3389/fimmu.2018.02582395459Single-Cell Transcriptomics in Cancer Immunobiology: The Future of Precision OncologyFatima Valdes-Mora0Fatima Valdes-Mora1Kristina Handler2Andrew M. K. Law3Robert Salomon4Samantha R. Oakes5Samantha R. Oakes6Christopher J. Ormandy7Christopher J. Ormandy8David Gallego-Ortega9David Gallego-Ortega10Genomics and Epigenetics Division, Garvan Institute of Medical Research, Darlinghurst, NSW, AustraliaSt. Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW, AustraliaThe Kinghorn Cancer Centre, Garvan Institute of Medical Research, Darlinghurst, NSW, AustraliaThe Kinghorn Cancer Centre, Garvan Institute of Medical Research, Darlinghurst, NSW, AustraliaGarvan-Weizmann Centre for Cellular Genomics, Garvan Institute of Medical Research, Darlinghurst, NSW, AustraliaSt. Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW, AustraliaThe Kinghorn Cancer Centre, Garvan Institute of Medical Research, Darlinghurst, NSW, AustraliaSt. Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW, AustraliaThe Kinghorn Cancer Centre, Garvan Institute of Medical Research, Darlinghurst, NSW, AustraliaSt. Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Sydney, NSW, AustraliaThe Kinghorn Cancer Centre, Garvan Institute of Medical Research, Darlinghurst, NSW, AustraliaCancer is a heterogeneous and complex disease. Tumors are formed by cancer cells and a myriad of non-cancerous cell types that together with the extracellular matrix form the tumor microenvironment. These cancer-associated cells and components contribute to shape the progression of cancer and are deeply involved in patient outcome. The immune system is an essential part of the tumor microenvironment, and induction of cancer immunotolerance is a necessary step involved in tumor formation and growth. Immune mechanisms are intimately associated with cancer progression, invasion, and metastasis; as well as to tumor dormancy and modulation of sensitivity to drug therapy. Transcriptome analyses have been extensively used to understand the heterogeneity of tumors, classifying tumors into molecular subtypes and establishing signatures that predict response to therapy and patient outcomes. However, the classification of the tumor cell diversity and specially the identification of rare populations has been limited in these transcriptomic analyses of bulk tumor cell populations. Massively-parallel single-cell RNAseq analysis has emerged as a powerful method to unravel heterogeneity and to study rare cell populations in cancer, through unsupervised sampling and modeling of transcriptional states in single cells. In this context, the study of the role of the immune system in cancer would benefit from single cell approaches, as it will enable the characterization and/or discovery of the cell types and pathways involved in cancer immunotolerance otherwise missed in bulk transcriptomic information. Thus, the analysis of gene expression patterns at single cell resolution holds the potential to provide key information to develop precise and personalized cancer treatment including immunotherapy. This review is focused on the latest single-cell RNAseq methodologies able to agnostically study thousands of tumor cells as well as targeted single-cell RNAseq to study rare populations within tumors. In particular, we will discuss methods to study the immune system in cancer. We will also discuss the current challenges to the study of cancer at the single cell level and the potential solutions to the current approaches.https://www.frontiersin.org/article/10.3389/fimmu.2018.02582/fullScRNA-seqtumor immunologyMDSCstumor heterogeneitystromasingle-cell transcriptomics
spellingShingle Fatima Valdes-Mora
Fatima Valdes-Mora
Kristina Handler
Andrew M. K. Law
Robert Salomon
Samantha R. Oakes
Samantha R. Oakes
Christopher J. Ormandy
Christopher J. Ormandy
David Gallego-Ortega
David Gallego-Ortega
Single-Cell Transcriptomics in Cancer Immunobiology: The Future of Precision Oncology
Frontiers in Immunology
ScRNA-seq
tumor immunology
MDSCs
tumor heterogeneity
stroma
single-cell transcriptomics
title Single-Cell Transcriptomics in Cancer Immunobiology: The Future of Precision Oncology
title_full Single-Cell Transcriptomics in Cancer Immunobiology: The Future of Precision Oncology
title_fullStr Single-Cell Transcriptomics in Cancer Immunobiology: The Future of Precision Oncology
title_full_unstemmed Single-Cell Transcriptomics in Cancer Immunobiology: The Future of Precision Oncology
title_short Single-Cell Transcriptomics in Cancer Immunobiology: The Future of Precision Oncology
title_sort single cell transcriptomics in cancer immunobiology the future of precision oncology
topic ScRNA-seq
tumor immunology
MDSCs
tumor heterogeneity
stroma
single-cell transcriptomics
url https://www.frontiersin.org/article/10.3389/fimmu.2018.02582/full
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