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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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 |
work_keys_str_mv |
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