Expression of PD-1/PD-L1 in esophageal squamous cell carcinoma and its relationship with survival prognosis: A systematic review and meta-analysis_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

YU Qiyao ,  LI Bin , FENG Haiming , LIN Junping , YIN Ci , LI Zheng , LI Xuan , SUN Yiming , MAO Wenjie , LI Jie , XIAO Cui

Department of Thoracic Surgery, Lanzhou University Second Hospital, Lanzhou University Second Clinical Medical College, Lanzhou, 730030, P.R.China;

Corresponding author：

LI Bin, Email: dr.leebin@outlook.com

Keywords：

Esophageal squamous cell carcinoma; programmed cell death receptor 1; programmed cell death ligand 1; prognosis; systematic review/meta-analysis

DOI：

10.7507/1007-4848.202008021

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

Objective To systematically evaluate the expression of programmed cell death receptor 1 (PD-1) and programmed cell death ligand 1 (PD-L1) in esophageal squamous cell carcinoma and its relationship with prognosis.Methods The literature from PubMed, EMbase, The Cochrane Library, Web of Science, CNKI and Wanfang data from inception to February 22, 2020 was searched by computer. Data were extracted and the quality of literature was evaluated using RevMan 5.3 software for meta-analysis. Egger's and Begg's tests were used to evaluate publication bias, and Stata 15.1 software was used for sensitivity analysis.Results A total of 16 articles were included, and there were 3 378 patients with esophageal squamous cell carcinoma. The methodological index for nonrandomized studies (MINORS) scores were all 12 points and above. The meta-analysis results showed that the positive expression rates of PD-1 and PD-L1 in tumor cells were 37.8% (190/504) and 41.7% (1 407/3 378), respectively. The positive expression of PD-L1 in tumor immune infiltrating cells was 41.7% (412/987). The overall survival (OS) of the tumor cell with high PD-L1 expression was lower than that with low PD-LI expression (HR=1.30, 95%CI 1.01-1.69, P=0.04). The OS of the tumor immune infiltrating cell with high PD-L1 expression was significantly higher than that with low PD-LI expression (HR=0.65, 95%CI 0.53-0.80, P<0.0001).Conclusion PD-L1 has a high expression rate in esophageal squamous cell carcinoma and is an important factor for the prognosis of esophageal squamous cell carcinoma.

Citation： YU Qiyao, LI Bin, FENG Haiming, LIN Junping, YIN Ci, LI Zheng, LI Xuan, SUN Yiming, MAO Wenjie, LI Jie, XIAO Cui. Expression of PD-1/PD-L1 in esophageal squamous cell carcinoma and its relationship with survival prognosis: A systematic review and meta-analysis. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2021, 28(11): 1352-1359. doi: 10.7507/1007-4848.202008021 Copy

1.	Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2018, 68(6): 394-424.
2.	Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015. CA Cancer J Clin, 2016, 66(2): 115-132.
3.	McDermott DF, Atkins MB. PD-1 as a potential target in cancer therapy. Cancer Med, 2013, 2(5): 662-673.
4.	Cohen DJ, Leichman L. Controversies in the treatment of local and locally advanced gastric and esophageal cancers. J Clin Oncol, 2015, 33(16): 1754-1759.
5.	Kleinberg L, Forastiere AA. Chemoradiation in the management of esophageal cancer. J Clin Oncol, 2007, 25(26): 4110-4117.
6.	Zou W, Chen L. Inhibitory B7-family molecules in the tumour microenvironment. Nat Rev Immunol, 2008, 8(6): 467-477.
7.	Sharma P, Allison JP. The future of immune checkpoint therapy. Science, 2015, 348(6230): 56-61.
8.	Dubinski D, Wölfer J, Hasselblatt M, et al. CD4⁺ T effector memory cell dysfunction is associated with the accumulation of granulocytic myeloid-derived suppressor cells in glioblastoma patients. Neuro Oncol, 2016, 18(6): 807-818.
9.	Jiang Y, Lo AWI, Wong A, et al. Prognostic significance of tumor-infiltrating immune cells and PD-L1 expression in esophageal squamous cell carcinoma. Oncotarget, 2017, 8(18): 30175-30189.
10.	Chen K, Cheng G, Zhang F, et al. Prognostic significance of programmed death-1 and programmed death-ligand 1 expression in patients with esophageal squamous cell carcinoma. Oncotarget, 2016, 7(21): 30772-30780.
11.	Zhao JJ, Zhou ZQ, Wang P, et al. Orchestration of immune checkpoints in tumor immune contexture and their prognostic significance in esophageal squamous cell carcinoma. Cancer Manag Res, 2018, 10: 6457-6468.
12.	Chen L, Deng H, Lu M, et al. B7-H1 expression associates with tumor invasion and predicts patient's survival in human esophageal cancer. Int J Clin Exp Pathol, 2014, 7(9): 6015-6023.
13.	Chen MF, Chen PT, Chen WC, et al. The role of PD-L1 in the radiation response and prognosis for esophageal squamous cell carcinoma related to IL-6 and T-cell immunosuppression. Oncotarget, 2016, 7(7): 7913-7924.
14.	Fukuoka E, Yamashita K, Tanaka T, et al. Neoadjuvant chemotherapy increases PD-L1 expression and CD8⁺ tumor-infiltrating lymphocytes in esophageal squamous cell carcinoma. Anticancer Res, 2019, 39(8): 4539-4548.
15.	Hatogai K, Kitano S, Fujii S, et al. Comprehensive immunohistochemical analysis of tumor microenvironment immune status in esophageal squamous cell carcinoma. Oncotarget, 2016, 7(30): 47252-47264.
16.	Jesinghaus M, Steiger K, Slotta-Huspenina J, et al. Increased intraepithelial CD3⁺ T-lymphocytes and high PD-L1 expression on tumor cells are associated with a favorable prognosis in esophageal squamous cell carcinoma and allow prognostic immunogenic subgrouping. Oncotarget, 2017, 8(29): 46756-46768.
17.	Kim R, Keam B, Kwon D, et al. Programmed death ligand-1 expression and its prognostic role in esophageal squamous cell carcinoma. World J Gastroenterol, 2016, 22(37): 8389-8397.
18.	Leng C, Li Y, Qin J, et al. Relationship between expression of PD-L1 and PD-L2 on esophageal squamous cell carcinoma and the antitumor effects of CD8⁺T cells. Oncol Rep, 2016, 35(2): 699-708.
19.	Rong L, liu Y, Hui Z, et al. PD-L1 expression and its clinicopathological correlation in advanced esophageal squamous cell carcinoma in a Chinese population. Diagn Pathol, 2019, 14(1): 6.
20.	Tanaka K, Miyata H, Sugimura K, et al. Negative influence of programmed death-1-ligands on the survival of esophageal cancer patients treated with chemotherapy. Cancer Sci, 2016, 107(6): 726-733.
21.	Tsutsumi S, Saeki H, Nakashima Y, et al. Programmed death-ligand 1 expression at tumor invasive front is associated with epithelial-mesenchymal transition and poor prognosis in esophageal squamous cell carcinoma. Cancer Sci, 2017, 108(6): 1119-1127.
22.	Zhang W, Pang Q, Zhang X, et al. Programmed death-ligand 1 is prognostic factor in esophageal squamous cell carcinoma and is associated with epidermal growth factor receptor. Cancer Sci, 2017, 108(4): 590-597.
23.	Zhu Y, Li M, Mu D, et al. CD8⁺/FOXP3⁺ ratio and PD-L1 expression associated with survival in pT3N0M0 stage esophageal squamous cell cancer. Oncotarget, 2016, 7(44): 71455-71465.
24.	Jiang D, Song Q, Wang H, et al. Independent prognostic role of PD-L1 expression in patients with esophageal squamous cell carcinoma. Oncotarget, 2017, 8(5): 8315-8329.
25.	Guo W, Wang P, Li N, et al. Prognostic value of PD-L1 in esophageal squamous cell carcinoma: A meta-analysis. Oncotarget, 2017, 9(17): 13920-13933.
26.	Zimmerman MP, Mehr SR. Targeted programmed cell death in lung cancer treatment. Am J Manag Care, 2014, 20(5 Spec No.): E3.
27.	Velcheti V, Schalper KA, Carvajal DE, et al. Programmed death ligand-1 expression in non-small cell lung cancer. Lab Invest, 2014, 94(1): 107-116.
28.	Schalper KA, Velcheti V, Carvajal D, et al. In situ tumor PD-L1 mRNA expression is associated with increased TILs and better outcome in breast carcinomas. Clin Cancer Res, 2014, 20(10): 2773-2782.
29.	Taube JM, Anders RA, Young GD, et al. Colocalization of inflammatory response with B7-h1 expression in human melanocytic lesions supports an adaptive resistance mechanism of immune escape. Sci Transl Med, 2012, 4(127): 127ra37.
30.	Droeser RA, Hirt C, Viehl CT, et al. Clinical impact of programmed cell death ligand 1 expression in colorectal cancer. Eur J Cancer, 2013, 49(9): 2233-2242.
31.	Brambilla E, Le Teuff G, Marguet S, et al. Prognostic effect of tumor lymphocytic infiltration in resectable non-small-cell lung cancer. J Clin Oncol, 2016, 34(11): 1223-1230.

1. Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2018, 68(6): 394-424.
2. Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015. CA Cancer J Clin, 2016, 66(2): 115-132.
3. McDermott DF, Atkins MB. PD-1 as a potential target in cancer therapy. Cancer Med, 2013, 2(5): 662-673.
4. Cohen DJ, Leichman L. Controversies in the treatment of local and locally advanced gastric and esophageal cancers. J Clin Oncol, 2015, 33(16): 1754-1759.
5. Kleinberg L, Forastiere AA. Chemoradiation in the management of esophageal cancer. J Clin Oncol, 2007, 25(26): 4110-4117.
6. Zou W, Chen L. Inhibitory B7-family molecules in the tumour microenvironment. Nat Rev Immunol, 2008, 8(6): 467-477.
7. Sharma P, Allison JP. The future of immune checkpoint therapy. Science, 2015, 348(6230): 56-61.
8. Dubinski D, Wölfer J, Hasselblatt M, et al. CD4⁺ T effector memory cell dysfunction is associated with the accumulation of granulocytic myeloid-derived suppressor cells in glioblastoma patients. Neuro Oncol, 2016, 18(6): 807-818.
9. Jiang Y, Lo AWI, Wong A, et al. Prognostic significance of tumor-infiltrating immune cells and PD-L1 expression in esophageal squamous cell carcinoma. Oncotarget, 2017, 8(18): 30175-30189.
10. Chen K, Cheng G, Zhang F, et al. Prognostic significance of programmed death-1 and programmed death-ligand 1 expression in patients with esophageal squamous cell carcinoma. Oncotarget, 2016, 7(21): 30772-30780.
11. Zhao JJ, Zhou ZQ, Wang P, et al. Orchestration of immune checkpoints in tumor immune contexture and their prognostic significance in esophageal squamous cell carcinoma. Cancer Manag Res, 2018, 10: 6457-6468.
12. Chen L, Deng H, Lu M, et al. B7-H1 expression associates with tumor invasion and predicts patient's survival in human esophageal cancer. Int J Clin Exp Pathol, 2014, 7(9): 6015-6023.
13. Chen MF, Chen PT, Chen WC, et al. The role of PD-L1 in the radiation response and prognosis for esophageal squamous cell carcinoma related to IL-6 and T-cell immunosuppression. Oncotarget, 2016, 7(7): 7913-7924.
14. Fukuoka E, Yamashita K, Tanaka T, et al. Neoadjuvant chemotherapy increases PD-L1 expression and CD8⁺ tumor-infiltrating lymphocytes in esophageal squamous cell carcinoma. Anticancer Res, 2019, 39(8): 4539-4548.
15. Hatogai K, Kitano S, Fujii S, et al. Comprehensive immunohistochemical analysis of tumor microenvironment immune status in esophageal squamous cell carcinoma. Oncotarget, 2016, 7(30): 47252-47264.
16. Jesinghaus M, Steiger K, Slotta-Huspenina J, et al. Increased intraepithelial CD3⁺ T-lymphocytes and high PD-L1 expression on tumor cells are associated with a favorable prognosis in esophageal squamous cell carcinoma and allow prognostic immunogenic subgrouping. Oncotarget, 2017, 8(29): 46756-46768.
17. Kim R, Keam B, Kwon D, et al. Programmed death ligand-1 expression and its prognostic role in esophageal squamous cell carcinoma. World J Gastroenterol, 2016, 22(37): 8389-8397.
18. Leng C, Li Y, Qin J, et al. Relationship between expression of PD-L1 and PD-L2 on esophageal squamous cell carcinoma and the antitumor effects of CD8⁺T cells. Oncol Rep, 2016, 35(2): 699-708.
19. Rong L, liu Y, Hui Z, et al. PD-L1 expression and its clinicopathological correlation in advanced esophageal squamous cell carcinoma in a Chinese population. Diagn Pathol, 2019, 14(1): 6.
20. Tanaka K, Miyata H, Sugimura K, et al. Negative influence of programmed death-1-ligands on the survival of esophageal cancer patients treated with chemotherapy. Cancer Sci, 2016, 107(6): 726-733.
21. Tsutsumi S, Saeki H, Nakashima Y, et al. Programmed death-ligand 1 expression at tumor invasive front is associated with epithelial-mesenchymal transition and poor prognosis in esophageal squamous cell carcinoma. Cancer Sci, 2017, 108(6): 1119-1127.
22. Zhang W, Pang Q, Zhang X, et al. Programmed death-ligand 1 is prognostic factor in esophageal squamous cell carcinoma and is associated with epidermal growth factor receptor. Cancer Sci, 2017, 108(4): 590-597.
23. Zhu Y, Li M, Mu D, et al. CD8⁺/FOXP3⁺ ratio and PD-L1 expression associated with survival in pT3N0M0 stage esophageal squamous cell cancer. Oncotarget, 2016, 7(44): 71455-71465.
24. Jiang D, Song Q, Wang H, et al. Independent prognostic role of PD-L1 expression in patients with esophageal squamous cell carcinoma. Oncotarget, 2017, 8(5): 8315-8329.
25. Guo W, Wang P, Li N, et al. Prognostic value of PD-L1 in esophageal squamous cell carcinoma: A meta-analysis. Oncotarget, 2017, 9(17): 13920-13933.
26. Zimmerman MP, Mehr SR. Targeted programmed cell death in lung cancer treatment. Am J Manag Care, 2014, 20(5 Spec No.): E3.
27. Velcheti V, Schalper KA, Carvajal DE, et al. Programmed death ligand-1 expression in non-small cell lung cancer. Lab Invest, 2014, 94(1): 107-116.
28. Schalper KA, Velcheti V, Carvajal D, et al. In situ tumor PD-L1 mRNA expression is associated with increased TILs and better outcome in breast carcinomas. Clin Cancer Res, 2014, 20(10): 2773-2782.
29. Taube JM, Anders RA, Young GD, et al. Colocalization of inflammatory response with B7-h1 expression in human melanocytic lesions supports an adaptive resistance mechanism of immune escape. Sci Transl Med, 2012, 4(127): 127ra37.
30. Droeser RA, Hirt C, Viehl CT, et al. Clinical impact of programmed cell death ligand 1 expression in colorectal cancer. Eur J Cancer, 2013, 49(9): 2233-2242.
31. Brambilla E, Le Teuff G, Marguet S, et al. Prognostic effect of tumor lymphocytic infiltration in resectable non-small-cell lung cancer. J Clin Oncol, 2016, 34(11): 1223-1230.

Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Expression of PD-1/PD-L1 in esophageal squamous cell carcinoma and its relationship with survival prognosis: A systematic review and meta-analysis

Abstract Full text Figures/Tables Video References Cited by

Previous Article

Next Article

Format

Content