Neoadjuvant immunotherapy for colorectal cancer: Right regimens, right patients, right directions?
Neoadjuvant chemoradiotherapy (NACRT) or chemotherapy (NACT) followed by radical resection and then adjuvant therapy is considered the optimal treatment model for locally advanced colorectal cancer (LACRC). A recent total neoadjuvant therapy (TNT) strategy further improved the tumour regression rate...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-03-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1120684/full |
| _version_ | 1811159581241376768 |
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| author | Jiahao Zhu Jie Lian Benjie Xu Xiangyi Pang Shengjun Ji Yutian Zhao Haibo Lu |
| author_facet | Jiahao Zhu Jie Lian Benjie Xu Xiangyi Pang Shengjun Ji Yutian Zhao Haibo Lu |
| author_sort | Jiahao Zhu |
| collection | DOAJ |
| description | Neoadjuvant chemoradiotherapy (NACRT) or chemotherapy (NACT) followed by radical resection and then adjuvant therapy is considered the optimal treatment model for locally advanced colorectal cancer (LACRC). A recent total neoadjuvant therapy (TNT) strategy further improved the tumour regression rate preoperatively and reduced local-regional recurrence in locally advanced rectal cancer (LARC). However, distant metastasis was still high, and little overall survival benefit was obtained from these preoperative treatment models. According to mismatch repair protein expression, MSI-H/dMMR and non-MSI-H/pMMR statuses were defined in colorectal cancer (CRC) patients. Due to the special features of biologics in MSI-H/dMMR CRC patients, this subgroup of patients achieved little treatment efficacy from chemoradiotherapy but benefited from immune checkpoint inhibitors (ICIs). The KEYNOTE-177 trial observed favourable survival outcomes in metastatic CRC patients treated with one-line pembrolizumab with tolerable toxicity. Given the better systemic immune function, increased antigenic exposure, and improved long-term memory induction before surgery, neoadjuvant ICI (NAICI) treatment was proposed. The NICHE trial pioneered the use of NAICI treatment in LACRC, and recent reports from several phase II studies demonstrated satisfactory tumour downsizing in CRC. Preclinical rationales and preliminary early-phase human trials reveal the feasibility of NAICI therapy and the therapeutic efficacy provided by this treatment model. Better tumour regression before surgery also increases the possibility of organ preservation for low LARC. However, the optimal treatment strategy and effective biomarker identification for beneficiary selection remain unknown, and potential pitfalls exist, including tumour progression during neoadjuvant treatment due to drug resistance and surgery delay. Given these foundations and questions, further phase II or III trials with large samples need to be conducted to explore the right regimens for the right patients. |
| first_indexed | 2024-04-10T05:44:44Z |
| format | Article |
| id | doaj.art-d49fe080be424747bada122ac6e405ae |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-10T05:44:44Z |
| publishDate | 2023-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-d49fe080be424747bada122ac6e405ae2023-03-06T05:07:48ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-03-011410.3389/fimmu.2023.11206841120684Neoadjuvant immunotherapy for colorectal cancer: Right regimens, right patients, right directions?Jiahao Zhu0Jie Lian1Benjie Xu2Xiangyi Pang3Shengjun Ji4Yutian Zhao5Haibo Lu6Department of Outpatient Chemotherapy, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, ChinaDepartment of Outpatient Chemotherapy, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, ChinaDepartment of Outpatient Chemotherapy, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, ChinaDepartment of Outpatient Chemotherapy, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, ChinaDepartment of Radiotherapy and Oncology, The Affiliated Suzhou Hospital of Nanjing Medical University, Gusu School, Nanjing Medical University, Suzhou, Jiangsu, ChinaDepartment of Radiotherapy and Oncology, The Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, ChinaDepartment of Outpatient Chemotherapy, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, ChinaNeoadjuvant chemoradiotherapy (NACRT) or chemotherapy (NACT) followed by radical resection and then adjuvant therapy is considered the optimal treatment model for locally advanced colorectal cancer (LACRC). A recent total neoadjuvant therapy (TNT) strategy further improved the tumour regression rate preoperatively and reduced local-regional recurrence in locally advanced rectal cancer (LARC). However, distant metastasis was still high, and little overall survival benefit was obtained from these preoperative treatment models. According to mismatch repair protein expression, MSI-H/dMMR and non-MSI-H/pMMR statuses were defined in colorectal cancer (CRC) patients. Due to the special features of biologics in MSI-H/dMMR CRC patients, this subgroup of patients achieved little treatment efficacy from chemoradiotherapy but benefited from immune checkpoint inhibitors (ICIs). The KEYNOTE-177 trial observed favourable survival outcomes in metastatic CRC patients treated with one-line pembrolizumab with tolerable toxicity. Given the better systemic immune function, increased antigenic exposure, and improved long-term memory induction before surgery, neoadjuvant ICI (NAICI) treatment was proposed. The NICHE trial pioneered the use of NAICI treatment in LACRC, and recent reports from several phase II studies demonstrated satisfactory tumour downsizing in CRC. Preclinical rationales and preliminary early-phase human trials reveal the feasibility of NAICI therapy and the therapeutic efficacy provided by this treatment model. Better tumour regression before surgery also increases the possibility of organ preservation for low LARC. However, the optimal treatment strategy and effective biomarker identification for beneficiary selection remain unknown, and potential pitfalls exist, including tumour progression during neoadjuvant treatment due to drug resistance and surgery delay. Given these foundations and questions, further phase II or III trials with large samples need to be conducted to explore the right regimens for the right patients.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1120684/fullcolorectal cancerimmune checkpoint blockadeimmunotherapymicrosatellite instabilityneoadjuvant treatment |
| spellingShingle | Jiahao Zhu Jie Lian Benjie Xu Xiangyi Pang Shengjun Ji Yutian Zhao Haibo Lu Neoadjuvant immunotherapy for colorectal cancer: Right regimens, right patients, right directions? Frontiers in Immunology colorectal cancer immune checkpoint blockade immunotherapy microsatellite instability neoadjuvant treatment |
| title | Neoadjuvant immunotherapy for colorectal cancer: Right regimens, right patients, right directions? |
| title_full | Neoadjuvant immunotherapy for colorectal cancer: Right regimens, right patients, right directions? |
| title_fullStr | Neoadjuvant immunotherapy for colorectal cancer: Right regimens, right patients, right directions? |
| title_full_unstemmed | Neoadjuvant immunotherapy for colorectal cancer: Right regimens, right patients, right directions? |
| title_short | Neoadjuvant immunotherapy for colorectal cancer: Right regimens, right patients, right directions? |
| title_sort | neoadjuvant immunotherapy for colorectal cancer right regimens right patients right directions |
| topic | colorectal cancer immune checkpoint blockade immunotherapy microsatellite instability neoadjuvant treatment |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1120684/full |
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