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Review

Hyperprogression Under Immune Checkpoint-Based Immunotherapy—Current Understanding, The Role of PD-1/PD-L1 Tumour-Intrinsic Signalling, Future Directions and a Potential Large Animal Model

1
International Centre for Cancer Vaccine Science, University of Gdansk, Wita Stwosza 63, 80-308 Gdansk, Poland
2
The Royal (Dick) School of Veterinary Studies and The Roslin Institute, University of Edinburgh, Easter Bush Campus, Midlothian EH25 9RG, UK
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Cancers 2020, 12(4), 804; https://doi.org/10.3390/cancers12040804
Received: 18 February 2020 / Revised: 22 March 2020 / Accepted: 23 March 2020 / Published: 27 March 2020
(This article belongs to the Special Issue New Insights into Cancer Vaccines and Immunotherapy)
Immune evasion is a major challenge for the development of successful cancer treatments. One of the known mechanisms is the expression of immune checkpoints (ICs)—proteins regulating the immune cells activation. The advent of immunotherapy using monoclonal antibodies (mAbs) to block the immune checkpoint receptor-ligand interaction brought about a landslide improvement in the treatment responses, leading to a prompt approval of such therapeutics. In recent years, it was discovered that a subset of patients receiving IC blockade treatment experienced a previously unknown pattern of treatment response called hyperprogression (HP), characterised by rapid deterioration on initialisation of the therapy. HP represents an urgent issue for clinicians and drug developers, while posing questions about the adequacy of the current clinical trial process. Here, we briefly summarise the state of knowledge and propose new directions for research into HP mechanisms, focusing on tumour-intrinsic signalling of IC proteins malignantly expressed by cancer. We also discuss the potential role of spontaneously occurring canine cancer in the assessment of immunotherapeutics, which can provide the missing link between murine and human studies. View Full-Text
Keywords: hyperprogression; hyperprogressive disease; tumour-intrinsic signalling; cancer; immunotherapy; comparative oncology; canine model; immune checkpoint blockade; PD-1; PD-L1 hyperprogression; hyperprogressive disease; tumour-intrinsic signalling; cancer; immunotherapy; comparative oncology; canine model; immune checkpoint blockade; PD-1; PD-L1
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MDPI and ACS Style

Kocikowski, M.; Dziubek, K.; Parys, M. Hyperprogression Under Immune Checkpoint-Based Immunotherapy—Current Understanding, The Role of PD-1/PD-L1 Tumour-Intrinsic Signalling, Future Directions and a Potential Large Animal Model. Cancers 2020, 12, 804. https://doi.org/10.3390/cancers12040804

AMA Style

Kocikowski M, Dziubek K, Parys M. Hyperprogression Under Immune Checkpoint-Based Immunotherapy—Current Understanding, The Role of PD-1/PD-L1 Tumour-Intrinsic Signalling, Future Directions and a Potential Large Animal Model. Cancers. 2020; 12(4):804. https://doi.org/10.3390/cancers12040804

Chicago/Turabian Style

Kocikowski, Mikolaj, Katarzyna Dziubek, and Maciej Parys. 2020. "Hyperprogression Under Immune Checkpoint-Based Immunotherapy—Current Understanding, The Role of PD-1/PD-L1 Tumour-Intrinsic Signalling, Future Directions and a Potential Large Animal Model" Cancers 12, no. 4: 804. https://doi.org/10.3390/cancers12040804

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