A landscape of checkpoint blockade resistance in cancer: underlying mechanisms and current strategies to overcome resistance

The discovery of immune checkpoints and the development of immune checkpoint inhibitors (ICI) have achieved a durable response in advanced-stage cancer patients. However, there is still a high proportion of patients who do not benefit from ICI therapy due to a lack of response when first treated (pr...

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Main Authors: Ginette S. Santiago-Sánchez, Kellsye P. Fabian, James W. Hodge
Format: Article
Language:English
Published: Taylor & Francis Group 2024-12-01
Series:Cancer Biology & Therapy
Subjects:
Online Access:https://www.tandfonline.com/doi/10.1080/15384047.2024.2308097
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author Ginette S. Santiago-Sánchez
Kellsye P. Fabian
James W. Hodge
author_facet Ginette S. Santiago-Sánchez
Kellsye P. Fabian
James W. Hodge
author_sort Ginette S. Santiago-Sánchez
collection DOAJ
description The discovery of immune checkpoints and the development of immune checkpoint inhibitors (ICI) have achieved a durable response in advanced-stage cancer patients. However, there is still a high proportion of patients who do not benefit from ICI therapy due to a lack of response when first treated (primary resistance) or detection of disease progression months after objective response is observed (acquired resistance). Here, we review the current FDA-approved ICI for the treatment of certain solid malignancies, evaluate the contrasting responses to checkpoint blockade in different cancer types, explore the known mechanisms associated with checkpoint blockade resistance (CBR), and assess current strategies in the field that seek to overcome these mechanisms. In order to improve current therapies and develop new ones, the immunotherapy field still has an unmet need in identifying other molecules that act as immune checkpoints, and uncovering other mechanisms that promote CBR.
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issn 1538-4047
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publishDate 2024-12-01
publisher Taylor & Francis Group
record_format Article
series Cancer Biology & Therapy
spelling doaj-art-b071a3a9e19246f28522f4937fb9cd672025-08-20T02:49:46ZengTaylor & Francis GroupCancer Biology & Therapy1538-40471555-85762024-12-0125110.1080/15384047.2024.2308097A landscape of checkpoint blockade resistance in cancer: underlying mechanisms and current strategies to overcome resistanceGinette S. Santiago-Sánchez0Kellsye P. Fabian1James W. Hodge2Center for Immuno-Oncology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USACenter for Immuno-Oncology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USACenter for Immuno-Oncology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USAThe discovery of immune checkpoints and the development of immune checkpoint inhibitors (ICI) have achieved a durable response in advanced-stage cancer patients. However, there is still a high proportion of patients who do not benefit from ICI therapy due to a lack of response when first treated (primary resistance) or detection of disease progression months after objective response is observed (acquired resistance). Here, we review the current FDA-approved ICI for the treatment of certain solid malignancies, evaluate the contrasting responses to checkpoint blockade in different cancer types, explore the known mechanisms associated with checkpoint blockade resistance (CBR), and assess current strategies in the field that seek to overcome these mechanisms. In order to improve current therapies and develop new ones, the immunotherapy field still has an unmet need in identifying other molecules that act as immune checkpoints, and uncovering other mechanisms that promote CBR.https://www.tandfonline.com/doi/10.1080/15384047.2024.2308097Immune checkpoint inhibitors (ICI)immune checkpoint blockadecheckpoint blockade resistanceimmunotherapy resistancecheckpoint blockade resistance mechanisms
spellingShingle Ginette S. Santiago-Sánchez
Kellsye P. Fabian
James W. Hodge
A landscape of checkpoint blockade resistance in cancer: underlying mechanisms and current strategies to overcome resistance
Cancer Biology & Therapy
Immune checkpoint inhibitors (ICI)
immune checkpoint blockade
checkpoint blockade resistance
immunotherapy resistance
checkpoint blockade resistance mechanisms
title A landscape of checkpoint blockade resistance in cancer: underlying mechanisms and current strategies to overcome resistance
title_full A landscape of checkpoint blockade resistance in cancer: underlying mechanisms and current strategies to overcome resistance
title_fullStr A landscape of checkpoint blockade resistance in cancer: underlying mechanisms and current strategies to overcome resistance
title_full_unstemmed A landscape of checkpoint blockade resistance in cancer: underlying mechanisms and current strategies to overcome resistance
title_short A landscape of checkpoint blockade resistance in cancer: underlying mechanisms and current strategies to overcome resistance
title_sort landscape of checkpoint blockade resistance in cancer underlying mechanisms and current strategies to overcome resistance
topic Immune checkpoint inhibitors (ICI)
immune checkpoint blockade
checkpoint blockade resistance
immunotherapy resistance
checkpoint blockade resistance mechanisms
url https://www.tandfonline.com/doi/10.1080/15384047.2024.2308097
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