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Neoadjuvant Immunotherapy for MSI-H/dMMR Locally Advanced Colorectal Cancer: New Strategies and Unveiled Opportunities

Patients with locally advanced colorectal cancer (LACRC) have a high risk of recurrence and metastasis, although neoadjuvant therapy may provide some benefit. However, patients with high microsatellite instability/deficient mismatch repair (MSI-H/dMMR) LACRC receive little benefit from neoadjuvant c...

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Autores principales: Zhang, Xuan, Wu, Tao, Cai, Xinyi, Dong, Jianhua, Xia, Cuifeng, Zhou, Yongchun, Ding, Rong, Yang, Renfang, Tan, Jing, Zhang, Lijuan, Zhang, Ya, Wang, Yuqin, Dong, Chao, Li, Yunfeng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8968082/
https://www.ncbi.nlm.nih.gov/pubmed/35371084
http://dx.doi.org/10.3389/fimmu.2022.795972
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author Zhang, Xuan
Wu, Tao
Cai, Xinyi
Dong, Jianhua
Xia, Cuifeng
Zhou, Yongchun
Ding, Rong
Yang, Renfang
Tan, Jing
Zhang, Lijuan
Zhang, Ya
Wang, Yuqin
Dong, Chao
Li, Yunfeng
author_facet Zhang, Xuan
Wu, Tao
Cai, Xinyi
Dong, Jianhua
Xia, Cuifeng
Zhou, Yongchun
Ding, Rong
Yang, Renfang
Tan, Jing
Zhang, Lijuan
Zhang, Ya
Wang, Yuqin
Dong, Chao
Li, Yunfeng
author_sort Zhang, Xuan
collection PubMed
description Patients with locally advanced colorectal cancer (LACRC) have a high risk of recurrence and metastasis, although neoadjuvant therapy may provide some benefit. However, patients with high microsatellite instability/deficient mismatch repair (MSI-H/dMMR) LACRC receive little benefit from neoadjuvant chemoradiotherapy (nCRT) or neoadjuvant chemotherapy (nCT). The 2015 KEYNOTE-016 trial identified MSI-H/dMMR as a biomarker indicative of immunotherapy efficacy, and pointed to the potential use of immune checkpoint inhibitors (ICIs). In 2017, the FDA approved two ICIs (pembrolizumab and nivolumab) for treatment of MSI-H/dMMR metastatic CRC (mCRC). In 2018, the CheckMate-142 trial demonstrated successful treatment of mCRC based on “double immunity” provided by nivolumab with ipilimumab, a regimen that may become a standard first-line treatment for MSI-H mCRC. In 2018, the FDA approved nivolumab alone or with ipilimumab for patients who progressed to MSI-H/dMMR mCRC after standard chemotherapy. The FDA then approved pembrolizumab alone as a first-line treatment for patients with MSI-H/dMMR CRC that was unresectable or metastatic. There is now interest in using these drugs in neoadjuvant immunotherapy (nIT) for patients with MSI-H/dMMR non-mCRC. In 2020, the NICHE trial marked the start of using nIT for CRC. This novel treatment of MSI-H/dMMR LACRC may change the approaches used for neoadjuvant therapy of other cancers. Our review of immunotherapy for CRC covers diagnosis and treatment, clinical prognostic characteristics, the mechanism of nIT, analysis of completed prospective and retrospective studies, and ongoing clinical trials, and the clinical practice of using nIT for MSI-H/dMMR LACRC. Our team also proposes a new organ-preservation strategy for patients with MSI-H/dMMR low LARC.
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spelling pubmed-89680822022-04-01 Neoadjuvant Immunotherapy for MSI-H/dMMR Locally Advanced Colorectal Cancer: New Strategies and Unveiled Opportunities Zhang, Xuan Wu, Tao Cai, Xinyi Dong, Jianhua Xia, Cuifeng Zhou, Yongchun Ding, Rong Yang, Renfang Tan, Jing Zhang, Lijuan Zhang, Ya Wang, Yuqin Dong, Chao Li, Yunfeng Front Immunol Immunology Patients with locally advanced colorectal cancer (LACRC) have a high risk of recurrence and metastasis, although neoadjuvant therapy may provide some benefit. However, patients with high microsatellite instability/deficient mismatch repair (MSI-H/dMMR) LACRC receive little benefit from neoadjuvant chemoradiotherapy (nCRT) or neoadjuvant chemotherapy (nCT). The 2015 KEYNOTE-016 trial identified MSI-H/dMMR as a biomarker indicative of immunotherapy efficacy, and pointed to the potential use of immune checkpoint inhibitors (ICIs). In 2017, the FDA approved two ICIs (pembrolizumab and nivolumab) for treatment of MSI-H/dMMR metastatic CRC (mCRC). In 2018, the CheckMate-142 trial demonstrated successful treatment of mCRC based on “double immunity” provided by nivolumab with ipilimumab, a regimen that may become a standard first-line treatment for MSI-H mCRC. In 2018, the FDA approved nivolumab alone or with ipilimumab for patients who progressed to MSI-H/dMMR mCRC after standard chemotherapy. The FDA then approved pembrolizumab alone as a first-line treatment for patients with MSI-H/dMMR CRC that was unresectable or metastatic. There is now interest in using these drugs in neoadjuvant immunotherapy (nIT) for patients with MSI-H/dMMR non-mCRC. In 2020, the NICHE trial marked the start of using nIT for CRC. This novel treatment of MSI-H/dMMR LACRC may change the approaches used for neoadjuvant therapy of other cancers. Our review of immunotherapy for CRC covers diagnosis and treatment, clinical prognostic characteristics, the mechanism of nIT, analysis of completed prospective and retrospective studies, and ongoing clinical trials, and the clinical practice of using nIT for MSI-H/dMMR LACRC. Our team also proposes a new organ-preservation strategy for patients with MSI-H/dMMR low LARC. Frontiers Media S.A. 2022-03-17 /pmc/articles/PMC8968082/ /pubmed/35371084 http://dx.doi.org/10.3389/fimmu.2022.795972 Text en Copyright © 2022 Zhang, Wu, Cai, Dong, Xia, Zhou, Ding, Yang, Tan, Zhang, Zhang, Wang, Dong and Li https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Zhang, Xuan
Wu, Tao
Cai, Xinyi
Dong, Jianhua
Xia, Cuifeng
Zhou, Yongchun
Ding, Rong
Yang, Renfang
Tan, Jing
Zhang, Lijuan
Zhang, Ya
Wang, Yuqin
Dong, Chao
Li, Yunfeng
Neoadjuvant Immunotherapy for MSI-H/dMMR Locally Advanced Colorectal Cancer: New Strategies and Unveiled Opportunities
title Neoadjuvant Immunotherapy for MSI-H/dMMR Locally Advanced Colorectal Cancer: New Strategies and Unveiled Opportunities
title_full Neoadjuvant Immunotherapy for MSI-H/dMMR Locally Advanced Colorectal Cancer: New Strategies and Unveiled Opportunities
title_fullStr Neoadjuvant Immunotherapy for MSI-H/dMMR Locally Advanced Colorectal Cancer: New Strategies and Unveiled Opportunities
title_full_unstemmed Neoadjuvant Immunotherapy for MSI-H/dMMR Locally Advanced Colorectal Cancer: New Strategies and Unveiled Opportunities
title_short Neoadjuvant Immunotherapy for MSI-H/dMMR Locally Advanced Colorectal Cancer: New Strategies and Unveiled Opportunities
title_sort neoadjuvant immunotherapy for msi-h/dmmr locally advanced colorectal cancer: new strategies and unveiled opportunities
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8968082/
https://www.ncbi.nlm.nih.gov/pubmed/35371084
http://dx.doi.org/10.3389/fimmu.2022.795972
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