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Genetic Alterations and Checkpoint Expression: Mechanisms and Models for Drug Discovery

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Book cover Regulation of Cancer Immune Checkpoints

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1248))

Abstract

In this chapter, we will sketch a story that begins with the breakdown of chromosome homeostasis and genomic stability. Genomic alterations may render tumor cells eternal life at the expense of immunogenicity. Although antitumor immunity can be primed through neoantigens or inflammatory signals, tumor cells have evolved countermeasures to evade immune surveillance and strike back by modulating immune checkpoint related pathways. At present, monoclonal antibody drugs targeting checkpoints like PD-1 and CTLA-4 have significantly prolonged the survival of a variety of cancer patients, and thus have marked a great achievement in the history of antitumor therapy. Nevertheless, this is not the end of the story. As the relationship between genomic alteration and checkpoint expression is being delineated though the advances of preclinical animal models and emerging technologies, novel checkpoint targets are on the way to be discovered.

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  1. The State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animals for Disease Study, Department of Rheumatology and Immunology, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Model Animal Research Center of Nanjing University, Nanjing, Jiangsu, 210061, China

    Shuai Ding, Siqi Li, Shujie Zhang & Yan Li

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  1. Shuai Ding
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  2. Siqi Li
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Correspondence to Yan Li .

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  1. Institutes of Biomedical Sciences, Zhongshan-Xuhui Hospital, Fudan University, Shanghai, China

    Jie Xu

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Ding, S., Li, S., Zhang, S., Li, Y. (2020). Genetic Alterations and Checkpoint Expression: Mechanisms and Models for Drug Discovery. In: Xu, J. (eds) Regulation of Cancer Immune Checkpoints. Advances in Experimental Medicine and Biology, vol 1248. Springer, Singapore. https://doi.org/10.1007/978-981-15-3266-5_10

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