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

Mikołaj Kocikowski , Katarzyna Dziubek , Maciej Parys


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.
Author Mikołaj Kocikowski (ICCVS)
Mikołaj Kocikowski,,
- International Centre for Cancer Vaccine Science
, Katarzyna Dziubek (ICCVS)
Katarzyna Dziubek,,
- International Centre for Cancer Vaccine Science
, Maciej Parys (ICCVS)
Maciej Parys,,
- International Centre for Cancer Vaccine Science
Journal seriesCancers, ISSN 2072-6694, (N/A 140 pkt)
Issue year2020
Publication size in sheets0.9
Article number804
Keywords in Englishhyperprogression, hyperprogressive disease, tumour-intrinsic signalling, cancer, immunotherapy, comparative oncology, canine model, immune checkpoint blockade, PD-1, PD-L1
ASJC Classification2730 Oncology; 1306 Cancer Research
URL https://www.mdpi.com/2072-6694/12/4/804/pdf
Languageen angielski
LicenseJournal (articles only); published final; Uznanie Autorstwa (CC-BY); with publication
Score (nominal)140
Score sourcejournalList
ScoreMinisterial score = 140.0, 30-04-2020, ArticleFromJournal
Publication indicators Scopus SNIP (Source Normalised Impact per Paper): 2018 = 1.44; WoS Impact Factor: 2018 = 6.162 (2)
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