Resistance to PD1/PDL1 checkpoint inhibition

O'Donnell, Jake S., Long, Georgina V., Scolyer, Richard A., Teng, Michele W. L. and Smyth, Mark J. (2017) Resistance to PD1/PDL1 checkpoint inhibition. Cancer Treatment Reviews, 52 71-81. doi:10.1016/j.ctrv.2016.11.007

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Author O'Donnell, Jake S.
Long, Georgina V.
Scolyer, Richard A.
Teng, Michele W. L.
Smyth, Mark J.
Title Resistance to PD1/PDL1 checkpoint inhibition
Journal name Cancer Treatment Reviews   Check publisher's open access policy
ISSN 1532-1967
Publication date 2017-01-01
Year available 2016
Sub-type Critical review of research, literature review, critical commentary
DOI 10.1016/j.ctrv.2016.11.007
Open Access Status File (Author Post-print)
Volume 52
Start page 71
End page 81
Total pages 11
Place of publication London, United Kingdom
Publisher W. B. Saunders
Language eng
Subject 2730 Oncology
2741 Radiology Nuclear Medicine and imaging
Abstract For the first time in decades, patients with difficult-to-treat cancers such as advanced stage metastatic melanoma are being offered a glimpse of hope in the form of immunotherapies. By targeting factors that foster the development and maintenance of an immunosuppressive microenvironment within tumors, these therapies release the brakes on the host's own immune system; allowing cure of disease. Indeed, phase III clinical trials have revealed that therapies such as ipilimumab and pembrolizumab which target the CTLA4 and PD-1 immune checkpoints, respectively, have raised the three-year survival of patients with melanoma to ∼70%, and overall survival (>5 years) to ∼30%. Despite this unprecedented efficacy, many patients fail to respond, and more concerning, some patients who demonstrate encouraging initial responses to immunotherapy, can acquire resistance over time. There is now an urgent need to identify mechanisms of resistance, to predict outcome and to identify targets for combination therapy. Here, with the aim of guiding future combination trials that target specific resistance mechanisms to immunotherapies, we have summarised and discussed the current understanding of mechanisms promoting resistance to anti-PD1/PDL1 therapies, and how combination strategies which target these pathways might yield better outcomes for patients.
Keyword Anti-PD1
Combination therapies
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Critical review of research, literature review, critical commentary
Collections: HERDC Pre-Audit
Faculty of Medicine
School of Clinical Medicine Publications
Admin Only - School of Clinical Medicine
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Citation counts: TR Web of Science Citation Count  Cited 31 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 30 times in Scopus Article | Citations
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