Emerging dynamics pathways of response and resistance to PD-1 and CTLA-4 blockade: tackling uncertainty by confronting complexity

Abstract Immune checkpoint inhibitors provide considerable therapeutic benefit in a range of solid cancers as well as in a subgroup of hematological malignancies. Response rates are however suboptimal, and despite considerable efforts, predicting response to immune checkpoint inhibitors ahead of the...

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Main Authors: Allan Relecom, Maysaloun Merhi, Varghese Inchakalody, Shahab Uddin, Darawan Rinchai, Davide Bedognetti, Said Dermime
Format: Article
Language:English
Published: BMC 2021-02-01
Series:Journal of Experimental & Clinical Cancer Research
Subjects:
Online Access:https://doi.org/10.1186/s13046-021-01872-3
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spelling doaj-04129910aa8f4e70a5800946c4b6eaaf2021-02-21T12:05:39ZengBMCJournal of Experimental & Clinical Cancer Research1756-99662021-02-0140111910.1186/s13046-021-01872-3Emerging dynamics pathways of response and resistance to PD-1 and CTLA-4 blockade: tackling uncertainty by confronting complexityAllan Relecom0Maysaloun Merhi1Varghese Inchakalody2Shahab Uddin3Darawan Rinchai4Davide Bedognetti5Said Dermime6Department of Medical Oncology, Translational Research Institute, National Center for Cancer Care and Research, Hamad Medical CorporationDepartment of Medical Oncology, Translational Research Institute, National Center for Cancer Care and Research, Hamad Medical CorporationDepartment of Medical Oncology, Translational Research Institute, National Center for Cancer Care and Research, Hamad Medical CorporationTranslational Research Institute & Dermatology Institute, Academic Health System, Hamad Medical CorporationCancer Research Program, Research Branch, Sidra MedicineCancer Research Program, Research Branch, Sidra MedicineDepartment of Medical Oncology, Translational Research Institute, National Center for Cancer Care and Research, Hamad Medical CorporationAbstract Immune checkpoint inhibitors provide considerable therapeutic benefit in a range of solid cancers as well as in a subgroup of hematological malignancies. Response rates are however suboptimal, and despite considerable efforts, predicting response to immune checkpoint inhibitors ahead of their administration in a given patient remains elusive. The study of the dynamics of the immune system and of the tumor under immune checkpoint blockade brought insight into the mechanisms of action of these therapeutic agents. Equally relevant are the mechanisms of adaptive resistance to immune checkpoint inhibitors that have been uncovered through this approach. In this review, we discuss the dynamics of the immune system and of the tumor under immune checkpoint blockade emanating from recent studies on animal models and humans. We will focus on mechanisms of action and of resistance conveying information predictive of therapeutic response.https://doi.org/10.1186/s13046-021-01872-3Dynamics biomarkersImmune checkpoint inhibitorsPD-1CTLA-4TregsMDSCs
collection DOAJ
language English
format Article
sources DOAJ
author Allan Relecom
Maysaloun Merhi
Varghese Inchakalody
Shahab Uddin
Darawan Rinchai
Davide Bedognetti
Said Dermime
spellingShingle Allan Relecom
Maysaloun Merhi
Varghese Inchakalody
Shahab Uddin
Darawan Rinchai
Davide Bedognetti
Said Dermime
Emerging dynamics pathways of response and resistance to PD-1 and CTLA-4 blockade: tackling uncertainty by confronting complexity
Journal of Experimental & Clinical Cancer Research
Dynamics biomarkers
Immune checkpoint inhibitors
PD-1
CTLA-4
Tregs
MDSCs
author_facet Allan Relecom
Maysaloun Merhi
Varghese Inchakalody
Shahab Uddin
Darawan Rinchai
Davide Bedognetti
Said Dermime
author_sort Allan Relecom
title Emerging dynamics pathways of response and resistance to PD-1 and CTLA-4 blockade: tackling uncertainty by confronting complexity
title_short Emerging dynamics pathways of response and resistance to PD-1 and CTLA-4 blockade: tackling uncertainty by confronting complexity
title_full Emerging dynamics pathways of response and resistance to PD-1 and CTLA-4 blockade: tackling uncertainty by confronting complexity
title_fullStr Emerging dynamics pathways of response and resistance to PD-1 and CTLA-4 blockade: tackling uncertainty by confronting complexity
title_full_unstemmed Emerging dynamics pathways of response and resistance to PD-1 and CTLA-4 blockade: tackling uncertainty by confronting complexity
title_sort emerging dynamics pathways of response and resistance to pd-1 and ctla-4 blockade: tackling uncertainty by confronting complexity
publisher BMC
series Journal of Experimental & Clinical Cancer Research
issn 1756-9966
publishDate 2021-02-01
description Abstract Immune checkpoint inhibitors provide considerable therapeutic benefit in a range of solid cancers as well as in a subgroup of hematological malignancies. Response rates are however suboptimal, and despite considerable efforts, predicting response to immune checkpoint inhibitors ahead of their administration in a given patient remains elusive. The study of the dynamics of the immune system and of the tumor under immune checkpoint blockade brought insight into the mechanisms of action of these therapeutic agents. Equally relevant are the mechanisms of adaptive resistance to immune checkpoint inhibitors that have been uncovered through this approach. In this review, we discuss the dynamics of the immune system and of the tumor under immune checkpoint blockade emanating from recent studies on animal models and humans. We will focus on mechanisms of action and of resistance conveying information predictive of therapeutic response.
topic Dynamics biomarkers
Immune checkpoint inhibitors
PD-1
CTLA-4
Tregs
MDSCs
url https://doi.org/10.1186/s13046-021-01872-3
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