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Cancer-Associated Fibroblasts and T Cells: From Mechanisms to Outcomes

Alfie T. Baker, Mohammed H. Abuwarwar, Lylarath Poly, Simon Wilkins and Anne L. Fletcher
J Immunol January 15, 2021, 206 (2) 310-320; DOI: https://doi.org/10.4049/jimmunol.2001203
Alfie T. Baker
*Department of Biochemistry and Molecular Biology, Monash Biomedicine Discovery Institute, Monash University, Clayton 3800, Victoria, Australia;
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Mohammed H. Abuwarwar
*Department of Biochemistry and Molecular Biology, Monash Biomedicine Discovery Institute, Monash University, Clayton 3800, Victoria, Australia;
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Lylarath Poly
*Department of Biochemistry and Molecular Biology, Monash Biomedicine Discovery Institute, Monash University, Clayton 3800, Victoria, Australia;
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Simon Wilkins
†Cabrini Monash University Department of Surgery, Cabrini Hospital, Malvern 3144, Victoria, Australia;
‡Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne 3004, Victoria, Australia; and
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Anne L. Fletcher
*Department of Biochemistry and Molecular Biology, Monash Biomedicine Discovery Institute, Monash University, Clayton 3800, Victoria, Australia;
§Institute of Immunology and Immunotherapy, University of Birmingham, Edgbaston B15 2TT, United Kingdom
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Abstract

Over the past decade, T cell immunotherapy has changed the face of cancer treatment, providing robust treatment options for several previously intractable cancers. Unfortunately, many epithelial tumors with high mortality rates respond poorly to immunotherapy, and an understanding of the key impediments is urgently required. Cancer-associated fibroblasts (CAFs) comprise the most frequent nonneoplastic cellular component in most solid tumors. Far from an inert scaffold, CAFs significantly influence tumor neogenesis, persistence, and metastasis and are emerging as a key player in immunotherapy resistance. In this review, we discuss the physical and chemical barriers that CAFs place between effector T cells and their tumor cell targets, and the therapies poised to target them.

Footnotes

  • This work was supported by a Monash Graduate Scholarship (to A.T.B.), a Monash Fellowship (to A.L.F.), the Saudi Arabian Cultural Mission, affiliate to the Royal Embassy of Saudi Arabia in Australia, and Ministry of Education, Saudi Arabia (to M.H.A.), Cabrini Foundation Research Grant ST081 (to S.W. and A.L.F.), and Let’s Beat Bowel Cancer (to S.W.). Funders played no role in manuscript preparation or content.

  • Abbreviations used in this article:

    CAF
    cancer-associated fibroblast
    CAR-T
    T cell with high-affinity chimeric Ag receptor
    CMS
    consensus molecular subtype
    ECM
    extracellular matrix
    FAP
    fibroblast activation protein
    myCAF
    myofibroblastic CAF
    NSCLC
    non–small cell lung cancer
    PDAC
    pancreatic ductal adenocarcinoma
    PD-L
    programmed death ligand
    PDPN
    podoplanin
    RNA-Seq
    RNA sequencing
    αSMA
    α smooth muscle actin
    TIL
    tumor-infiltrating lymphocyte
    TLT
    tertiary lymphoid tissue
    Treg
    regulatory T cell.

  • Received October 23, 2020.
  • Accepted November 6, 2020.
  • Copyright © 2021 by The American Association of Immunologists, Inc.
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The Journal of Immunology: 206 (2)
The Journal of Immunology
Vol. 206, Issue 2
15 Jan 2021
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Cancer-Associated Fibroblasts and T Cells: From Mechanisms to Outcomes
Alfie T. Baker, Mohammed H. Abuwarwar, Lylarath Poly, Simon Wilkins, Anne L. Fletcher
The Journal of Immunology January 15, 2021, 206 (2) 310-320; DOI: 10.4049/jimmunol.2001203

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Cancer-Associated Fibroblasts and T Cells: From Mechanisms to Outcomes
Alfie T. Baker, Mohammed H. Abuwarwar, Lylarath Poly, Simon Wilkins, Anne L. Fletcher
The Journal of Immunology January 15, 2021, 206 (2) 310-320; DOI: 10.4049/jimmunol.2001203
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