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Checkpoint Inhibitors in the Treatment of Metastatic Melanoma

Mechanisms of Resistance to Checkpoint Immunotherapy

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Cutaneous Melanoma

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Abstract

A better understanding of the mechanisms underlying cancer cells’ ability to evade and suppress the immune system have led to the development of immune checkpoint inhibitors, monoclonal antibodies that act to promote an effective antitumor immune response. CTLA-4 inhibitors, such as ipilimumab, and PD-1 inhibitors, such as pembrolizumab and nivolumab, have revolutionized the treatment of advanced melanoma, leading to dramatically improved patient outcomes and introducing the possibility of long-term survival. These agents are associated with response rates that range from 10% to 60%. While this represents a substantial improvement over standard cytotoxic chemotherapy, there is still a large subset of patients that exhibit either primary or secondary resistance to this treatment strategy. This chapter outlines the potential mechanisms behind resistance to checkpoint blockade, including factors involved in T-cell activation and recruitment as well as elements of the tumor microenvironment that play critical roles in effector T-cell function.

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Authors and Affiliations

  1. Peter MacCallum Cancer Centre, Melbourne, VIC, Australia

    Alison Weppler, Peter Lau & Grant McArthur

  2. University of Melbourne, Parkville, VIC, Australia

    Grant McArthur

Authors
  1. Alison Weppler
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  2. Peter Lau
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  3. Grant McArthur
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Corresponding author

Correspondence to Grant McArthur .

Editor information

Editors and Affiliations

  1. Division of Surgical Oncology, University of Texas Southwestern, Dallas, TX, USA

    Charles Balch

  2. Division of Surgery, UT MD Anderson Cancer Center, Houston, TX, USA

    Jeffrey Gershenwald

  3. Melanoma Institute of Australia, Wollstonecraft, Australia

    John Thompson

  4. Georgetown Medical Center, Washington, DC, USA

    Michael Atkins

  5. Melanoma and Skin Cancer Program, University of Pittsburgh, Pittsburgh, PA, USA

    John Kirkwood

  6. University of Sydney, Sydney, NSW, Australia

    Richard Kefford

  7. Department of Dermatology, Harvard Medical Center, Boston, MA, USA

    Arthur Sober

  8. Department of Dermatology, Memorial Sloan Kettering, New York, NY, USA

    Allan Halpern

  9. Department of Dermatology, University Hospital, TĂĽbingen, TĂĽbingen, Germany

    Claus Garbe

  10. Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown NSW, Australia

    Richard Scolyer

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Weppler, A., Lau, P., McArthur, G. (2019). Checkpoint Inhibitors in the Treatment of Metastatic Melanoma. In: Balch, C., et al. Cutaneous Melanoma. Springer, Cham. https://doi.org/10.1007/978-3-319-46029-1_39-1

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  • DOI: https://doi.org/10.1007/978-3-319-46029-1_39-1

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  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-46029-1

  • Online ISBN: 978-3-319-46029-1

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