• Jie Liu
  • Jie XuEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1248)


Cancer immunotherapy, especially immune checkpoint blockade therapy, represents a hotspot in cancer research. However, the low response rate, adaptive/acquired resistance, and adverse effects still keep most cancer patients from obtaining sustained clinical benefits. To overcome these limitations, it is essential to improve our understanding on the regulation of immune checkpoints under physiological and pathological contexts. Recent researches have gained insights into the molecular control of immune checkpoint receptors and ligands, which extended our knowledge on the immune system and provided alternative strategies for developing checkpoint inhibitors.


Immune checkpoint Cancer immunotherapy Gene regulation Biomarkers Antibody 


  1. Allison JP (2015) Immune checkpoint blockade in cancer therapy: the 2015 Lasker-DeBakey clinical medical research award. JAMA 314(11):1113–1114. PubMed PMID: 26348357Google Scholar
  2. Brahmer JR (2013) Harnessing the immune system for the treatment of non-small-cell lung cancer. J Clin Oncol 31(8):1021–1028. PubMed PMID: 23401435Google Scholar
  3. Byun DJ, Wolchok JD, Rosenberg LM, Girotra M (2017) Cancer immunotherapy - immune checkpoint blockade and associated endocrinopathies. Nat Rev Endocrinol 13(4):195–207. PubMed PMID: 28106152. Pubmed Central PMCID: 5629093Google Scholar
  4. Hafner A, Bulyk ML, Jambhekar A, Lahav G (2019) The multiple mechanisms that regulate p53 activity and cell fate. Nat Rev Mol Cell Biol 20(4):199–210. PubMed PMID: 30824861Google Scholar
  5. Hassounah NB, Malladi VS, Huang Y, Freeman SS, Beauchamp EM, Koyama S et al (2019) Identification and characterization of an alternative cancer-derived PD-L1 splice variant. Cancer Immunol Immunother: CII 68(3):407–420. PubMed PMID: 30564890. Pubmed Central PMCID: 6428600Google Scholar
  6. Kleffel S, Posch C, Barthel SR, Mueller H, Schlapbach C, Guenova E et al (2015) Melanoma cell-intrinsic PD-1 receptor functions promote tumor growth. Cell 162(6):1242–1256. PubMed PMID: 26359984. Pubmed Central PMCID: 4700833Google Scholar
  7. Li H, Li X, Liu S, Guo L, Zhang B, Zhang J et al (2017) Programmed cell death-1 (PD-1) checkpoint blockade in combination with a mammalian target of rapamycin inhibitor restrains hepatocellular carcinoma growth induced by hepatoma cell-intrinsic PD-1. Hepatology 66(6):1920–1933. PubMed PMID: 28732118Google Scholar
  8. Liang L, Wang H, Shi H, Li Z, Yao H, Bu Z et al (2018) A designed peptide targets two types of modifications of p 53 with anti-cancer activity. Cell Chem Biol 25(6):761–774 e5. PubMed PMID: 29681526Google Scholar
  9. Minton K (2014) T cell signalling: p53 controls the crowd. Nat Rev Immunol 14(6):358. PubMed PMID: 24810199Google Scholar
  10. Nishino M, Ramaiya NH, Hatabu H, Hodi FS (2017) Monitoring immune-checkpoint blockade: response evaluation and biomarker development. Nat Rev Clin Oncol 14(11):655–668. PubMed PMID: 28653677. Pubmed Central PMCID: 5650537Google Scholar
  11. Samaan MA, Pavlidis P, Papa S, Powell N, Irving PM (2018) Gastrointestinal toxicity of immune checkpoint inhibitors: from mechanisms to management. Nat Rev Gastroenterol Hepatol 15(4):222–234. PubMed PMID: 29512649Google Scholar
  12. Sury K, Perazella MA, Shirali AC (2018) Cardiorenal complications of immune checkpoint inhibitors. Nat Rev Nephrol 14(9):571–588. PubMed PMID: 30013100Google Scholar
  13. Tang J, Yu JX, Hubbard-Lucey VM, Neftelinov ST, Hodge JP, Lin Y (2018) Trial watch: the clinical trial landscape for PD1/PDL1 immune checkpoint inhibitors. Nat Rev Drug Discov 17(12):854–855. PubMed PMID: 30482962Google Scholar
  14. Villanueva MT (2017) Cancer immunotherapy: searching in the immune checkpoint black box. Nat Rev Drug Discov 16(9):599. PubMed PMID: 28799544Google Scholar
  15. Wang Y, Wang H, Yao H, Li C, Fang JY, Xu J (2018) Regulation of PD-L1: emerging routes for targeting tumor immune evasion. Front Pharmacol 9:536. PubMed PMID: 29910728. Pubmed Central PMCID: 5992436Google Scholar
  16. Webster RM (2014) The immune checkpoint inhibitors: where are we now? Nat Rev Drug Discov 13(12):883–884. PubMed PMID: 25345674Google Scholar
  17. Wykes MN, Lewin SR (2018) Immune checkpoint blockade in infectious diseases. Nat Rev Immunol 18(2):91–104. PubMed PMID: 28990586. Pubmed Central PMCID: 5991909Google Scholar
  18. Yao H, Wang H, Li C, Fang JY, Xu J (2018) Cancer cell-intrinsic PD-1 and implications in combinatorial immunotherapy. Front Immunol 9:1774. PubMed PMID: 30105035. Pubmed Central PMCID: 6077319Google Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2020

Authors and Affiliations

  1. 1.Department of Digestive Diseases, Huashan HospitalFudan UniversityShanghaiChina
  2. 2.Department of Immunology, State Key Laboratory of Genetic Engineering, Institutes of Biomedical SciencesFudan UniversityShanghaiChina
  3. 3.Institutes of Biomedical Sciences, Zhongshan-Xuhui HospitalFudan UniversityShanghaiChina

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