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Immunological Targets for Immunotherapy: Inhibitory T Cell Receptors

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Biomarkers for Immunotherapy of Cancer

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2055))

Abstract

Tumor development is characterized by the accumulation of mutational and epigenetic changes that transform normal cells and survival pathways into self-sustaining cells capable of untrammeled growth. Although multiple modalities including surgery, radiation, and chemotherapy are available for the treatment of cancer, the benefits conferred are often limited. The immune system is capable of specific, durable, and adaptable responses. However, cancers hijack immune mechanisms such as negative regulatory checkpoints that have evolved to limit inflammatory and immune responses to thwart effective antitumor immunity. The development of monoclonal antibodies against inhibitory receptors expressed by immune cells has produced durable responses in a broad array of advanced malignancies and heralded a new dawn in the cancer armamentarium. However, these remarkable responses are limited to a minority of patients and indications, highlighting the need for more effective and novel approaches. Preclinical and clinical studies with immune checkpoint blockade are exploring the therapeutic potential antibody-based therapy targeting multiple inhibitory receptors. In this chapter, we discuss the current understanding of the structure, ligand specificities, function, and signaling activities of various inhibitory receptors. Additionally, we discuss the current development status of various immune checkpoint inhibitors targeting these negative immune receptors and highlight conceptual gaps in knowledge.

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Acknowledgments

Funding: This work was supported by an academy industry award from the Melanoma Research Alliance and Merck (H.M.Z.), NCI grant P50 CA121973 (J.M.K.), a Cancer Center Foundation Genentech BioOncology™ Young Investigator Award, and a grant from the Harry J Lloyd Trust (D.D.).

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  1. Cancer Immunology and Immunotherapeutics Program (CIIP), Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, USA

    Diwakar Davar & Hassane M. Zarour

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  1. Diwakar Davar
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  2. Hassane M. Zarour
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Correspondence to Diwakar Davar .

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  1. NIH, National Cancer Institute, Bethesda, MD, USA

    Magdalena Thurin

  2. Nanostring Technologies, Seattle, WA, USA, ESSA Pharma, South San Francisco, CA, USA

    Alessandra Cesano

  3. Refuge Biotechnologies, Menlo Park, CA, USA

    Francesco M. Marincola

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Davar, D., Zarour, H.M. (2020). Immunological Targets for Immunotherapy: Inhibitory T Cell Receptors. In: Thurin, M., Cesano, A., Marincola, F. (eds) Biomarkers for Immunotherapy of Cancer. Methods in Molecular Biology, vol 2055. Humana, New York, NY. https://doi.org/10.1007/978-1-4939-9773-2_2

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