程序性死亡蛋白1及其配体在结直肠癌中的临床研究现状

doi:10.11904/j.issn.1002-3070.2021.04.014

摘要/Abstract

摘要： 程序性死亡蛋白-1(Programmed cell death protein-1,PD-1)通过与程序性死亡蛋白配体-1(Programmed cell death protein ligand-1,PD-L1)相互作用进而发挥负向调节机体免疫反应机制,促使肿瘤细胞发生免疫逃逸。以PD-1/PD-L1为靶点的免疫治疗已成为肿瘤治疗的新模式。目前,手术和放化疗仍然是结直肠癌的主要治疗手段,但生存率没有明显的改善。研究显示PD-1/PD-L1抑制剂单药治疗或与放化疗和手术联合治疗在结直肠癌中取得了可观的效果,且相关的临床试验正在进行。本文阐述了PD-1/PD-L1信号通路相关的分子生物学机制及PD-L1的表达与结直肠癌放化疗和预后的关系,并介绍了PD-1/PD-L1抑制剂在结直肠癌中的临床研究进展。

关键词: 程序性死亡蛋白-1/程序性死亡蛋白配体-1, 结直肠癌, 放化疗, 预后

Abstract: Programmed cell death protein-1(PD-1)plays a negative role in regulating immune response by interacting with programmed cell death protein ligand-1(PD-L1),which promotes tumor cell immune escape.Immunotherapy targeting PD-1/PD-L1 has become a new model of tumor therapy.At present,surgery and radiotherapy and chemotherapy are still the main treatment for colorectal cancer,but the survival rate has not been significantly improved.Studies have shown that PD-1/PD-L1 inhibitors alone or combined with radiotherapy,chemotherapy and surgery have achieved considerable results in colorectal cancer,and related clinical trials are ongoing.This article reviews the molecular biological mechanism of PD-1/PD-L1 signaling pathway and the relationship between the expression of PD-L1 and the chemoradiotherapy and prognosis of colorectal cancer,and introduces the clinical research progress of PD-1/PD-L1 inhibitors in colorectal cancer.

Key words: Programmed cell death protein-1/Programmed cell death protein ligand-1(PD-1/PD-L1), Colorectal cancer, Radiotherapy and chemotherapy, Prognosis

中图分类号:

R735.3⁺5

刘文, 乔文波. 程序性死亡蛋白1及其配体在结直肠癌中的临床研究现状[J]. 实用肿瘤学杂志, 2021, 35(4): 370-375.

LIU Wen, QIAO Wenbo. Clinical research status of programmed cell death protein-1 and its ligand in colorectal cancer[J]. Journal of Practical Oncology, 2021, 35(4): 370-375.

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链接本文: http://journal09.magtechjournal.com/Jwk3_syzlxzz/CN/10.11904/j.issn.1002-3070.2021.04.014

http://journal09.magtechjournal.com/Jwk3_syzlxzz/CN/Y2021/V35/I4/370

参考文献

1 Keum N,Giovannucci E.Global burden of colorectal cancer:emerging trends,risk factors and prevention strategies[J].Nat Rev Gastroenterol Hepatol,2019,16(12):713-732.
2 Eriksen AC,Sørensen FB,Lindebjerg J,et al.Programmed death ligand-1 expression in stage II colon cancer-experiences from a nationwide populationbased cohort[J].BMC Cancer,2019,19(1):142.
3 Chen Y,Gao M,Huang Z,et al.SBRT combined with PD-1/PD-L1 inhibitors in NSCLC treatment:a focus on the mechanisms,advances,and future challenges[J].J Hematol Oncol,2020,13(1):105.
4 Ni L,Lu J.Interferon gamma in cancer immunotherapy[J].Cancer Med,2018,7(9):4509-4516.
5 Zhang J,Dang F,Ren J,et al.Biochemical aspects of PD-L1 regulation in cancer immunotherapy[J].Trends Biochem Sci,2018,43(12):1014-1032.
6 Yang H,Zhang Q,Xu M,et al.CCL2-CCR2 axis recruits tumor associated macrophages to induce immune evasion through PD-1 signaling in esophageal carcinogenesis[J].Mol Cancer,2020,19(1):41.
7 Oliveira AF,Bretes L,Furtado I.Review of PD-1/PD-L1 inhibitors in metastatic dMMR/MSI-H colorectal cancer[J].Front Oncol,2019,9:396.
8 Pyo JS,Ko SH,Ko YS,et al.Clinicopathological significance of PD-L1 expression in colorectal cancer:impact of PD-L1 expression on pFOXO1 expression[J].Pathol Res Pract,2020,216(2):152764.
9 Kong P,Wang J,Song Z,et al.Circulating lymphocytes,PD-L1 expression on tumor-infiltrating lymphocytes,and survival of colorectal cancer patients with different mismatch repair gene status[J].J Cancer,2019,10(7):1745-1754.
10 Chiang SF,Huang CY,Ke TW,et al.Upregulation of tumor PD-L1 by neoadjuvant chemoradiotherapy(neoCRT)confers improved survival in patients with lymph node metastasis of locally advanced rectal cancers[J].Cancer Immunol Immunother,2019,68(2):283-296.
11 Shao L,Peng Q,Du K,et al.Tumor cell PD-L1 predicts poor local control for rectal cancer patients following neoadjuvant radiotherapy[J].Cancer Manag Res,2017,9:249-258.
12 Huang KC,Chiang SF,Chen WT,et al.Decitabine augments chemotherapy-induced PD-L1 upregulation for PD-L1 blockade in colorectal cancer[J].Cancers(Basel),2020,12(2):462.
13 Dosset M,Vargas TR,Lagrange A,et al.PD-1/PD-L1 pathway:an adaptive immune resistance mechanism to immunogenic chemotherapy in colorectal cancer[J].Oncoimmunology,2018,7(6):e1433981.
14 Ogura A,Akiyoshi T,Yamamoto N,et al.Pattern of programmed cell death-ligand 1 expression and CD8-positive T-cell infiltration before and after chemoradiotherapy in rectal cancer[J].Eur J Cancer,2018,91:11-20.
15 Chen TW,Huang KC,Chiang SF,et al.Prognostic relevance of programmed cell death-ligand 1 expression and CD8+ TILs in rectal cancer patients before and after neoadjuvant chemoradiotherapy[J].J Cancer Res Clin Oncol,2019,145(4):1043-1053.
16 Halmos B,Burke T,Kalyvas C,et al.A matching-adjusted indirect comparison of pembrolizumab + chemotherapy vs.nivolumab + ipilimumab as first-line therapies in patients with PD-L1 TPS ≥1% metastatic NSCLC[J].Cancers(Basel),2020,12(12):3648.
17 Yuan Z,Fromm A,Ahmed KA,et al.Radiotherapy rescue of a nivolumab-refractory immune response in a patient with PD-L1-negative metastatic squamous cell carcinoma of the lung[J].J Thorac Oncol,2017,12(9):135-136.
18 Tuminello S,Sikavi D,Veluswamy R,et al.PD-L1 as a prognostic biomarker in surgically resectable non-small cell lung cancer:a meta-analysis[J].Transl Lung Cancer Res,2020,9(4):1343-1360.
19 Ju C,Gao JC,Zhang PX,et al.Expression and significance of PD-1 and PD-L1 in the specimens of epithelial ovarian cancer[J].Zhonghua Fu Chan Ke Za Zhi,2020,55(8):529-534.
20 Ito M,Yajima S,Suzuki T,et al.High serum PD-L1 level is a poor prognostic biomarker in surgically treated esophageal cancer[J].Cancer Med,2020,9(4):1321-1327.
21 Zhao T,Li Y,Zhang J,et al.PD-L1 expression increased by IFN-γ via JAK2-STAT1 signaling and predicts a poor survival in colorectal cancer[J].Oncol Lett,2020,20(2):1127-1134.
22 Enkhbat T,Nishi M,Takasu C,et al.Programmed cell death ligand 1 expression is an independent prognostic factor in colorectal cancer[J].Anticancer Res,2018,38(6):3367-3373.
23 Berntsson J,Eberhard J,Nodin B,et al.Expression of programmed cell death protein 1(PD-1)and its ligand PD-L1 in colorectal cancer:relationship with sidedness and prognosis[J].Oncoimmunology,2018,7(8):e1465165.
24 Roach C,Zhang N,Corigliano E,et al.Development of a companion diagnostic PD-L1 immunohistochemistry assay for pembrolizumab therapy in non-small-cell lung cancer[J].Appl Immunohistochem Mol Morphol,2016,24(6):392-397.
25 Masugi Y,Nishihara R,Yang J,et al.Tumour CD274(PD-L1)expression and T cells in colorectal cancer[J].Gut,2017,66(8):1463-1473.
26 Le DT,Kim TW,Van Cutsem E,et al.Phase II open-label study of pembrolizumab in treatment-refractory,microsatellite instability-high/mismatch repair-deficient metastatic colorectal cancer:KEYNOTE-164[J].J Clin Oncol,2020,38(1):11-19.
27 Overman MJ,McDermott R,Leach JL,et al.Nivolumab in patients with metastatic DNA mismatch repair-deficient or microsatellite instability-high colorectal cancer(CheckMate 142):an open-label,multicentre,phase 2 study[J].Lancet Oncol,2017,18(9):1182-1191.
28 Kim JH,Kim SY,Baek JY,et al.A phase II study of avelumab monotherapy in patients with mismatch repair-deficient/microsatellite instability-high or pole-mutated metastatic or unresectable colorectal cancer[J].Cancer Res Treat,2020,52(4):1135-1144.
29 Horn L,Spigel DR,Vokes EE,et al.Nivolumab versus docetaxel in previously treated patients with advanced non-small-cell lung cancer:two-year outcomes from two randomized,open-label,phase III trials(CheckMate 017 and CheckMate 057)[J].J Clin Oncol,2017,35(35):3924-3933.
30 Zhang JJ,Zhang QS,Li ZQ,et al.Metformin attenuates PD-L1 expression through activating hippo signaling pathway in colorectal cancer cells[J].Am J Transl Res,2019,11(11):6965-6976.
31 侯建英,朱巍.免疫抑制剂PD-1/PD-L1治疗卵巢癌的研究进展[J].实用肿瘤学杂志,2020,34(3):266-270.
32 Yamamoto N,Nokihara H,Yamada Y,et al.Phase I study of nivolumab,an anti-PD-1 antibody,in patients with malignant solid tumors[J].Invest New Drugs,2017,35(2):207-216.
33 Rizvi NA,Hellmann MD,Brahmer JR,et al.Nivolumab in combination with platinum-based doublet chemotherapy for first-line rteatment of advanced non-small-cell lung cancer[J].J Clin Oncol,2016,34(25):2969-2979.

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