Biomarkers of Response and Resistance to Immunotherapy in Microsatellite Stable Colorectal Cancer: Toward a New Personalized Medicine

Immune Checkpoint Inhibitors (ICIs) are well recognized as a major immune treatment modality for multiple types of solid cancers. However, for colorectal cancer (CRC), ICIs are only approved for the treatment of Mismatch-Repair-Deficient and Microsatellite Instability-High (dMMR/MSI-H) tumors. For t...

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Main Authors: Nicolas Huyghe, Elena Benidovskaya, Philippe Stevens, Marc Van den Eynde
Format: Article
Language:English
Published: MDPI AG 2022-04-01
Series:Cancers
Subjects:
Online Access:https://www.mdpi.com/2072-6694/14/9/2241
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author Nicolas Huyghe
Elena Benidovskaya
Philippe Stevens
Marc Van den Eynde
author_facet Nicolas Huyghe
Elena Benidovskaya
Philippe Stevens
Marc Van den Eynde
author_sort Nicolas Huyghe
collection DOAJ
description Immune Checkpoint Inhibitors (ICIs) are well recognized as a major immune treatment modality for multiple types of solid cancers. However, for colorectal cancer (CRC), ICIs are only approved for the treatment of Mismatch-Repair-Deficient and Microsatellite Instability-High (dMMR/MSI-H) tumors. For the vast majority of CRC, that are not dMMR/MSI-H, ICIs alone provide limited to no clinical benefit. This discrepancy of response between CRC and other solid cancers suggests that CRC may be inherently resistant to ICIs alone. In translational research, efforts are underway to thoroughly characterize the immune microenvironment of CRC to better understand the mechanisms behind this resistance and to find new biomarkers of response. In the clinic, trials are being set up to study biomarkers along with treatments targeting newly discovered immune checkpoint molecules or treatments combining ICIs with other existing therapies to improve response in MSS CRC. In this review, we will focus on the characteristics of response and resistance to ICIs in CRC, and discuss promising biomarkers studied in recent clinical trials combining ICIs with other therapies.
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spelling doaj.art-4113bcfa3ee9410182647e0172a732c72023-11-23T07:56:50ZengMDPI AGCancers2072-66942022-04-01149224110.3390/cancers14092241Biomarkers of Response and Resistance to Immunotherapy in Microsatellite Stable Colorectal Cancer: Toward a New Personalized MedicineNicolas Huyghe0Elena Benidovskaya1Philippe Stevens2Marc Van den Eynde3Institut de Recherche Clinique et Expérimentale (Pole MIRO), UCLouvain, 1200 Brussels, BelgiumInstitut de Recherche Clinique et Expérimentale (Pole MIRO), UCLouvain, 1200 Brussels, BelgiumInstitut de Recherche Clinique et Expérimentale (Pole MIRO), UCLouvain, 1200 Brussels, BelgiumInstitut de Recherche Clinique et Expérimentale (Pole MIRO), UCLouvain, 1200 Brussels, BelgiumImmune Checkpoint Inhibitors (ICIs) are well recognized as a major immune treatment modality for multiple types of solid cancers. However, for colorectal cancer (CRC), ICIs are only approved for the treatment of Mismatch-Repair-Deficient and Microsatellite Instability-High (dMMR/MSI-H) tumors. For the vast majority of CRC, that are not dMMR/MSI-H, ICIs alone provide limited to no clinical benefit. This discrepancy of response between CRC and other solid cancers suggests that CRC may be inherently resistant to ICIs alone. In translational research, efforts are underway to thoroughly characterize the immune microenvironment of CRC to better understand the mechanisms behind this resistance and to find new biomarkers of response. In the clinic, trials are being set up to study biomarkers along with treatments targeting newly discovered immune checkpoint molecules or treatments combining ICIs with other existing therapies to improve response in MSS CRC. In this review, we will focus on the characteristics of response and resistance to ICIs in CRC, and discuss promising biomarkers studied in recent clinical trials combining ICIs with other therapies.https://www.mdpi.com/2072-6694/14/9/2241colorectal cancerimmunotherapyImmune Checkpoint Inhibitorsimmune checkpoint resistanceimmune microenvironmentbiomarker
spellingShingle Nicolas Huyghe
Elena Benidovskaya
Philippe Stevens
Marc Van den Eynde
Biomarkers of Response and Resistance to Immunotherapy in Microsatellite Stable Colorectal Cancer: Toward a New Personalized Medicine
Cancers
colorectal cancer
immunotherapy
Immune Checkpoint Inhibitors
immune checkpoint resistance
immune microenvironment
biomarker
title Biomarkers of Response and Resistance to Immunotherapy in Microsatellite Stable Colorectal Cancer: Toward a New Personalized Medicine
title_full Biomarkers of Response and Resistance to Immunotherapy in Microsatellite Stable Colorectal Cancer: Toward a New Personalized Medicine
title_fullStr Biomarkers of Response and Resistance to Immunotherapy in Microsatellite Stable Colorectal Cancer: Toward a New Personalized Medicine
title_full_unstemmed Biomarkers of Response and Resistance to Immunotherapy in Microsatellite Stable Colorectal Cancer: Toward a New Personalized Medicine
title_short Biomarkers of Response and Resistance to Immunotherapy in Microsatellite Stable Colorectal Cancer: Toward a New Personalized Medicine
title_sort biomarkers of response and resistance to immunotherapy in microsatellite stable colorectal cancer toward a new personalized medicine
topic colorectal cancer
immunotherapy
Immune Checkpoint Inhibitors
immune checkpoint resistance
immune microenvironment
biomarker
url https://www.mdpi.com/2072-6694/14/9/2241
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