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Review
. 2022 Sep 9:13:1001444.
doi: 10.3389/fimmu.2022.1001444. eCollection 2022.

Current progress and future perspectives of neoadjuvant anti-PD-1/PD-L1 therapy for colorectal cancer

Zhengyang Yang  1 , Guocong Wu  1 , Xiao Zhang  1 , Jiale Gao  1 , Cong Meng  1 , Yishan Liu  1 , Qi Wei  1 , Liting Sun  1 , Pengyu Wei  1 , Zhigang Bai  1 , Hongwei Yao  1 , Zhongtao Zhang  1
Affiliations
Review

Current progress and future perspectives of neoadjuvant anti-PD-1/PD-L1 therapy for colorectal cancer

Zhengyang Yang et al. Front Immunol. .

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.

Keywords: PD-1/PD-L1 inhibitors; colorectal cancer; microsatellite instability; mismatch repair; neoadjuvant.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Schematic mechanism of programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1) inhibitors to restore T-cell functions. T-cell receptor, antigen, and major histocompatibility complex (MHC). Reproduced with permission (40).
Figure 2
Figure 2
Schematic mechanism of radiotherapy enlarging anti-PD-1/PD-L1 curative effect. Damage-associated molecular patterns, cytotoxic T lymphocytes, antigen-presenting cell, and MHC. Reproduced with permission (72).
Figure 3
Figure 3
Calculation formula of the neoadjuvant rectal (NAR) score. NAR, pathologic nodal stage, clinical tumor stage, and pathologic tumor stage.
See this image and copyright information in PMC

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