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Published on: September 30, 2016
Current progress and future perspectives of neoadjuvant anti-PD-1/PD-L1 therapy for colorectal cancer
Zhengyang Yang1, Guocong Wu1, Xiao Zhang1
1Department of General Surgery, Beijing Friendship Hospital, Capital Medical University and National Clinical Research Center for Digestive Diseases, Beijing, China.
Abstract:
Immunotherapies, especially the programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1) inhibitors, have revolutionized the therapeutic strategies of various cancers. As for colorectal cancer (CRC), the current clinical application of PD-1/PD-L1 inhibitors are mainly used according to the mutation pattern, which is categorized into deficient mismatch repair (dMMR)/high levels of microsatellite instability (MSI-H) and proficient mismatch repair (pMMR), or non-high levels of microsatellite instability (non-MSI-H). PD-1/PD-L1 inhibitors have been proven to have favorable outcomes against dMMR/MSI-H CRC because of more T-cell infiltration into tumor tissues. Nevertheless, the effectiveness of PD-1/PD-L1 inhibitors in pMMR/non-MSI-H CRC is still uncertain. Because of the quite-lower proportion of dMMR/MSI-H in CRC, PD-1/PD-L1 inhibitors have been reported to combine with other antitumor treatments including chemotherapy, radiotherapy, and targeted therapy for better therapeutic effect in recent clinical trials. Neoadjuvant therapy, mainly including chemotherapy and radiotherapy, not only can reduce clinical stage but also benefit from local control, which can improve clinical symptoms and the quality of life. Adding immunotherapy into neoadjuvant therapy may change the treatment strategy of primary resectable or some metastatic CRC. In this review, we focus on the development of neoadjuvant anti-PD-1/PD-L1 therapy and discuss the future perspectives in CRC.
Insights
Programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1) inhibitors show promise in colorectal cancer (CRC), especially for dMMR/MSI-H subtypes. Combining these immunotherapies with neoadjuvant treatments may improve outcomes for broader CRC patient populations.
Area of Science:
- Oncology
- Immunology
- Cancer Therapeutics
Background:
- Immunotherapies, particularly PD-1/PD-L1 inhibitors, have transformed cancer treatment.
- In colorectal cancer (CRC), current PD-1/PD-L1 inhibitor use is stratified by mismatch repair deficiency (dMMR)/microsatellite instability-high (MSI-H) status.
- While effective in dMMR/MSI-H CRC, their efficacy in proficient mismatch repair (pMMR)/non-MSI-H CRC remains uncertain.
Purpose of the Study:
- To review the development of neoadjuvant anti-PD-1/PD-L1 therapy in colorectal cancer.
- To discuss the potential of combining immunotherapy with neoadjuvant chemotherapy and radiotherapy.
- To explore future perspectives for immunotherapy in CRC treatment strategies.
Main Methods:
- Literature review focusing on clinical trials and research regarding neoadjuvant anti-PD-1/PD-L1 therapy in CRC.
- Analysis of treatment outcomes based on CRC subtypes (dMMR/MSI-H vs. pMMR/non-MSI-H).
- Examination of combination strategies involving immunotherapy with chemotherapy, radiotherapy, and targeted therapy.
Main Results:
- PD-1/PD-L1 inhibitors demonstrate significant efficacy in dMMR/MSI-H CRC due to enhanced T-cell infiltration.
- Combinatorial approaches are being investigated to improve therapeutic effects in pMMR/non-MSI-H CRC.
- Neoadjuvant therapy, including chemotherapy and radiotherapy, can reduce clinical stage and improve local control.
Conclusions:
- Neoadjuvant anti-PD-1/PD-L1 therapy holds potential to alter treatment paradigms for resectable and metastatic CRC.
- Further research is needed to optimize immunotherapy combinations for diverse CRC patient groups.
- Integrating immunotherapy into neoadjuvant regimens may enhance clinical outcomes and quality of life for CRC patients.
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