The Fusion of Quantitative Molecular Proteomics and Immune-Oncology: A Step Towards Precision Medicine in Cancer Therapeutics

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Abstract

Innate and adaptive immune systems are built-in homeostatic functions of many multicellular organisms and protect the host against foreign pathogens and infections. Dysregulation of the molecular mechanisms of the immune system can result in autoimmune diseases. The immune system can also be harnessed and manipulated to provide targeted cancer therapies, some of them relying on the blockade of immune-checkpoint receptors. Two prominent immune checkpoints, PD-1/PD-L1 and CTLA-4/CD80, comprise receptor–ligand pairs that prevent the host immune cells from attacking host tissues. However, cancer cells upregulate the respective PD-L1 and CD80 ligands for PD-1 and CTLA-4 and thereby evade the host-immune response. Therapeutic drugs that block PD-1/PD-L1 and CTLA-4/CD80 interactions re-enable the immune system to attack cancer cells, but their prognostic biomarker remains challenging. In this review, we discuss how the use of quantitative molecular imaging can be exploited to predict the response to anti-PD-1/PD-L1 therapies and to identify cancer patients who would benefit from them.

Original languageEnglish
Pages (from-to)2721-2735
Number of pages15
JournalFEBS Letters
Volume596
Issue number21
Early online date24 Aug 2022
DOIs
Publication statusPublished - 30 Nov 2022

Bibliographical note

Funding Information:
We are most grateful to Professor Peter J Parker and the many years of his fruitful collaboration and discussions with our teams. We also thank Dr. Veronique Calleja, Dr. Lissete Sánchez‐Magraner and Mr. Christopher J Applebee for their crucial work which has led into the results discussed in this review [ 23 ]. Lastly, we are grateful to Mr. Pierre Leboucher for the initial and continued development of the semi‐automated high‐throughput image acquisition platform that was utilised in Veeriah et al., 2014, Miles et al., 2017 and Sánchez‐Magraner and Miles et al., 2020 [ 23,34,37 ]. All figures were created using BioRender. The work reviewed from the manuscript, Sanchez‐Magraner et al. (2020), was in part funded by the Bikaintek grant for industrial doctorates in the Basque Country. The work reviewed from Miles et al. (2017) acknowledges the funding from the Spanish Ministry of Economy for the grants (grant number BFU 2011‐28566) and Basque Government through the BERC 3602014–2017; the Spanish Ministry of Economy and Competitiveness (MINECO).

Keywords

  • CTLA-4/CD80
  • FRET/FLIM
  • PD-1/PD-L1
  • adaptive immunity
  • immune checkpoints
  • immune surveillance
  • innate immunity

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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