Tumour PD-L1 Expression in Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis
Abstract
1. Introduction
2. Materials and Methods
2.1. Search Strategy and Selection Criteria
2.2. Eligibility and Selection of Articles and Data Extraction
2.3. Data Analysis
3. Results
3.1. Prevalence of PD-L1 Expression in SCLC
3.2. Effect of PD-L1 Expression in Survival
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
Abbreviations
PD-L1 | Programmed cell death ligand-1 |
PD-1 | Programmed cell death-1 |
SCLC | Small-cell lung cancer |
NSCLC | Non-small cell lung cancer |
ED-SCLC | Extensive diseased staged SCLC |
TILS | Tumour infiltrating lymphocytes (TILs) |
IHC | Immunohistochemistry |
I2 | Heterogeneity |
OS | Overall survival |
HR | Hazard ratio |
References
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References (Sample Size) | Samples | Stage of Disease | Antibody | IHC/QIF Evaluation (%) | PD-L1 Positivity Rate (%) | Prognosis (Cut-off Value, mOS, HR and p-Value) |
---|---|---|---|---|---|---|
Ott et al. 2017 [23] (n = 145) | Biopsy tissue (n = 132) Fresh tissue (n = 12) | Extensive | Clone 22C3 antibody (Merck & Co, Kenilworth, NJ, USA) | Membranous ≥ 1% | 31.7% (46/145) | n/a |
Antonia et al., 2016 [25] (n = 213) | Biopsy tissue | Extensive | Clone 28-8; Epitomics Inc, Burlingame, CA, USA) | Membranous ≥ 1% | 11.3% (24/213) | n/a |
Yu et al., 2016 [28] (n = 249) | Biopsy tissue | Extensive (n = 96) Limited (n = 98) | Clone SP142 Dako clone 28.8 pharmDx kit | Membranous ≥ 1% | 16.5 (41/245) | ≥1% PD-L1/TPS, mOS: 9.87 vs. 16.13 months, Log rank test p = 0.0511 HR = 0.44 (95% CI 0.18–1.07, p = 0.055 |
Takada et al., 2016 [29] (n = 40) | Surgically-resected tissue | n/a | Clone E1L3N (Cell Signalling Technology, Cambridge, UK), | E1LN–membranous Allred, ≥1%, ≥5% | 22.5%, 27.5% 35.0% | N/E |
Clone 28.8 (Abcam Cambridge, UK) Clone SP142, Spring Bioscience, Ventana Tuscon, AZ, USA) | 28.8-membranous Allred, ≥1%, ≥5% SP142-membranous Allred, ≥1%, ≥5% | 20.5%, 27.0%, 32.5% 15.%, 15.0%, 15.0% | N/E | |||
Miao et al., 2017 [30] (n = 83) | Biopsy tissue | Extensive (n = 36) Limited (n = 47) | Clone 2B11D11/PD-L1/CD274 antibody, Clone SP66, SPRINGBIO, USA) | Membranous and/or cytoplasmic ≥ 5% | 51.8% (43/83) | ≥5% PD-L1/TPS (mOS, 17.0 vs. 9.0, Log rank test p = 0.018) HR not provided |
Komiya and Madan, 2015 [31] (n = 99) | Unknown | n/a | EPR1161 (Abcam, Cambridge, UK) | Membranous and/or cytoplasmic ≥ 5% | 82.8% (82/99) | NE |
Schultheis et al., 2015 [32] (n = 94) | Surgically-resected (n = 51), Biopsy (n = 43) | Extensive (n = 49), Limited (n = 49) | Clone 5H1 (Lieping Chen Laboratory, Yale University, New Haven, CT, USA) Clone E1L3N (Cell Signalling Technology, Cambridge, UK) | Membranous ≥ 1%, | 0.0% (0/94) | NE |
Yasuda et al., 2018 [33] (n = 39) | Biopsy tissue | Extensive | Clone 22C3 pharmDX (Agilent Technologies, Santa Clara, CA, USA) 22C3 (Dako, Carptintera, CA, USA) | Membranous ≥ 1% | 2.5% (1/39) | N/E |
Ishii et al., 2015 [34] (n = 102) | Biopsy tissue | Extensive (n = 61), Limited (n = 41) | EPR1161 (Abcam, Cambridge, UK) | Membranous and/or cell-surface ≥ 5% | 71.6% (73/102) | ≥5% PD-L1/TPS mOS: 16.3 vs. 7.3 months Log-rank test p < 0.001 HR not provided |
Pas-Ares et al., 2019 [43] (n = 277) | Biopsy tissue | Extensive | Clone SP263 Ventana PD-L1 Assay | Membranous ≥ 1% | 5.1 (14/277) | n/a |
Reck et al., 2020 [44] (n = 137) | Biopsy tissue | Extensive | Clone SP263 Ventana PD-L1 Assay | Membranous ≥ 1% | 5.8 (8/137) | n/a |
Carvajal-Hausdorf et al., 2019 [45] (n = 55) | n/a | Limited (n = 23) Extensive (n = 32) | Clone E1L3N (Cell Signalling Technology, Cambridge, UK), | Membranous and/or cytoplasmic ≥ 1% | 7.3% (4/55) | NE |
Chang et al., 2017 [46] (n = 186) | Biopsy tissue | Limited (n = 74) Extensive (112) | Clone 2B11D11, PD-L1/CD274 antibody (Cat/no.66248-1-Ig) Proteintech Group Inc Chicago, IL, USA | Membranous ≥ 5% | 78.0% (145/186) | HR = 0.17 (95% CI: 0.08–0.35, p < 0.001) |
Sun et al., 2019 [47] (n = 56) | Surgically-resected/biopsy tissue | Limited (n = 25) Extensive (n = 31) | Clone E1L3N, diluted 1:100; #13684, Cell Signalling Technology) | Membranous ≥ 5% | 39.3% (22/56) | Overall survival (OS) ≥ 5% HR = 0.37(95% CI: 0.21–0.68), p = 0.002 |
Inamura et al., 2017 [48] (n = 74) | Surgically-resected tissue | Extensive | Clone E1L3N (Cell Signalling Technology, Cambridge, UK), | Membranous ≥ 5% | 18.9% (14/74) | Lung-cancer-specific survival months, HR = 0.11 (95% CI: 0.006–0.52, p = 0.0020) Overall Survival (OS): HR = 0.19(95% CI: 0.10–1.30, p = 0.150) |
Tsuruoka et al., 2017 [49] (n = 65) | Biopsy/cytology | Limited | Clone E1L3N (Cell Signalling Technology, Cambridge, UK), | Membranous ≥ 1% | 5.8% (4/65) | ≥1% PD-L1/TPS, mOS (38 vs. 140 months) Log rank test p = 0.067) HR= 0.65(95% CI: 0.16–2.71, p = 0.557) |
Bonanno et al., 2018 [50] (n = 104) | Surgically-resected (n = 48) Biopsy tissue (n = 66) | Limited (n = 66) Extensive (n = 38) | Clone 22C3 (Dako, Carptintera, CA, USA) | Membranous ≥ 1% | 25.0% (26/104) | NE |
Berghoff et al., 2016 [51] (n = 32) | Biopsy tissue | Extensive | Clone 5H1 (Lieping Chen Laboratory, Yale University, USA) (Dako, Glostrup, Denmark) | Membranous ≥ 5% | 34.4 (11/32) | ≥5% PD-L1/TPS mOS: 8 vs. 7 months Log rank test p = 0.662 HR not provided |
Gadgeel et al., 2018 [52] (n = 30) | Biopsy tissue | Extensive | Clone 22C3 antibody (Dako, Carpinteria, CA, USA). | Membranous ≥ 1% | 10.0% (3/30) | n/a |
Kim et al. 2018 [53] (n = 120) | Biopsy tissue | Limited (n = 39) Extensive (n = 81) | MAB1561/B7-H1/PD-L1 antibody (R&D Systems, Minneapolis, MN, USA | Membranous ≥ 1% | 14.2% (17/120) | ≥1% PD-L1/TPS, mOS: 12.0 vs. 18.0 months, HR = 1.15 (95% CI 0.76–1.73, p = 0.510 |
Wang et al., 2018 [54] (n = 94) | Biopsy tissue | Extensive (n = 52) | Clone SP142; ZSGB-BIO, Beijing, China | Membranous and/or cytoplasmic ≥ 5% | 51.1% (48/94) | NE |
Ichiki et al., 2018 [55] (n = 46) | Surgically-resected | Limited (n = 12) Extensive (n = 34) | Clone E1L3N, 1:800, Cell Signalling Technology, Inc., Danvers, MA, USA) | Membranous ≥ 1% | 26.1% (12/46) | Overall Survival (OS): HR = 0.98 (0.94–1.02), p = 0.268 |
Liu et al., 2018 [56] (n = 80) | Surgically-resected | Limited (n = 80) | Clone SP142 (cat. no. 07309554001; 1:100; Spring Bioscience Corporation, Pleasanton, CA, USA | Membranous ≥ 5% | 65.0% (52/80) | Overall survival (OS) ≥ 5% HR = 0.49 (95% CI: 0.28–0.85), p = 0.0110 |
Chung et al. 2018 [57] (n = 107) | Biopsy tissue | Extensive | Clone 22C3 pharmDx assay (Agilent Technologies) | Membranous ≥ 1% | 39.0% (42/107) | n/a |
Xu et al., 2019 [58] (n = 60) | Surgically-resected | Limited (n = 20) Extensive (n = 40) | Clone 2B11D11 PD-L1/CD274 antibody (cat. no. 66248-1-Ig) (ProteinTech Group, Inc., Chicago, IL, USA) | Membranous and/or cytoplasmic ≥ 5% | 61.7% (37/60) | ≥5% PD-L1/TPS, mOS (22.13 vs. 22.03 months) Log rank test p = 0.781) HR = 2.55 (95% CI: 01.18–5.51), p = 0.017 |
Zhao et al., 2019 [59] (n = 155) | Surgically-resected | Limited (n = 52) Extensive (n = 103) | Clone 22C3, PharmDx | Membranous ≥ 1% | 12.9% (20/155) | ≥5% PD-L1/TPS, mOS (12 vs. 57 months, Lo g rank test p = 0.007) HR= 5.30 (95% CI: 1.45–19.28), p = 0.011 |
Pujol et al., 2018 [60] (n = 54) | Biopsy tissue | Extensive | SP142 PD-L1 immunohistochemistry assay (Ventana Medical Systems, Inc., Tucson, AZ, USA) | Membranous ≥ 1% | 1.8% (1/54) | n/a |
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Acheampong, E.; Abed, A.; Morici, M.; Bowyer, S.; Amanuel, B.; Lin, W.; Millward, M.; S. Gray, E. Tumour PD-L1 Expression in Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis. Cells 2020, 9, 2393. https://doi.org/10.3390/cells9112393
Acheampong E, Abed A, Morici M, Bowyer S, Amanuel B, Lin W, Millward M, S. Gray E. Tumour PD-L1 Expression in Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis. Cells. 2020; 9(11):2393. https://doi.org/10.3390/cells9112393
Chicago/Turabian StyleAcheampong, Emmanuel, Afaf Abed, Michael Morici, Samantha Bowyer, Benhur Amanuel, Weitao Lin, Michael Millward, and Elin S. Gray. 2020. "Tumour PD-L1 Expression in Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis" Cells 9, no. 11: 2393. https://doi.org/10.3390/cells9112393
APA StyleAcheampong, E., Abed, A., Morici, M., Bowyer, S., Amanuel, B., Lin, W., Millward, M., & S. Gray, E. (2020). Tumour PD-L1 Expression in Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis. Cells, 9(11), 2393. https://doi.org/10.3390/cells9112393