From Tumor Immunology to Immunotherapy in Gastric and Esophageal Cancer
Abstract
:1. Introduction
2. Molecular Subtypes of Esophageal and Gastric Cancer
3. Immune Checkpoints PD-1/PD-L1/PD-L2 and Clinical Significance in Gastric and Esophageal Cancer
3.1. PD-L1 Expression and Radiotherapy
3.2. PD-L1 Expression and Systemic Treatment
3.3. PD-L1 Expression and EBV Infection
3.4. PD-L1 Expression and MSI Status
3.5. PD-L1 Expression and Epithelial-Mesenchymal Transition Phenotype
3.6. PD-L1 Expression and EGFR
4. Significance of Microsatellite Instability
5. Immunotherapy
6. Conclusions
Funding
Conflicts of Interest
References
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Author | Number of Patients | Type of Cancer | Histology | Disease Stage | Percentage of PD-L1+ | Prognosis (PD-L1+) | Prognostic Value | Reference |
---|---|---|---|---|---|---|---|---|
Böger C et al. | 465 | gastric cancer | adenocarcinoma | all stages | tumor cells: 30.1% (primary cancer), 60% (liver metastases) immune cells: 88.4% (primary cancer), 73.3% (liver metastases) | better | improved OS and tumor specific survival | [12] |
Pereira MA et al. | 287 | gastric cancer | adenocarcinoma | all stages | 8.8% | no impact | no impact | [13] |
Tamura T et al. | 431 | gastric cancer | adenocarcinoma | all stages | 29.6% | worse | worse OS for stage II/III | [14] |
Zhang L et al. | 132 | gastric cancer | adenocarcinoma | II/III | 50.8% | worse | worse OS | [15] |
Eto S et al. | 105 | gastric cancer | adenocarcinoma | II/III | 24.7% | worse | worse OS (statistically non-significant) | [16] |
Tsutsumi et al. | 90 | esophageal cancer | SCC | localized | 36.6% | worse | worse OS and relapse free survival | [17] |
Kim R et al. | 200 | esophageal cancer | SCC | localized | 33.5% | worse | worse locoregional relapse rate and distant metastasis rate, no change in OS | [18] |
Zhang W et al. | 344 | esophageal cancer | SCC | II/III | tumor cells 14.5%, immune cells 24.7% | better | better OS and DFS only in immune cells PD-L1+ | [19] |
Zhu Y et al. | 133 | esophageal cancer | SCC | pT3pN0M0 | 42.1% | worse | worse DFS and OS | [20] |
Jiang Y et al. | 428 | esophageal cancer | SCC | localized and metastatic | 79.7% | worse | worse DFS and OS in radically treated patients | [21] |
Jesinghaus M et al. | 125 | esophageal cancer | SCC | all stages | 71% tumor cells, immune cells 87% | better | better OS, DSS and DFS (PD-L1+ tumor cells) | [22] |
Chen MF et al. | 162 | esophageal cancer | SCC | not specified | 45.7% | worse | worse treatment response and OS | [23] |
Kawazoe A et al. | 487 | gastric cancer | adenocarcinoma | localized | tumor cells 22.8%, immune cells 61.4 | no impact | no impact | [24] |
Thompson ED et al. | 34 | gastric cancer | adenocarcinoma | localized | tumor cells 12%, immune cells 44% | worse | worse PFS and OS | [25] |
Yang JH et al. | 72 | gastric cancer | adenocarcinoma | IV | 58.3% | better | better PFS | [26] |
Seo AN et al. | 116 | gastric cancer | adenocarcinoma | localized | tumor cells 49.1%, stromal cells 56.9% | worse | worse DFS, not OS | [27] |
Ito S et al. | 90 | esophageal cancer | SCC | localized | 19% | worse | worse OS | [28] |
Hsieh CC et al. | 150 | esophageal cancer | SCC | localized | 64% | worse | worse DFS | [29] |
Kollmann D et al. | 168 | esophageal cancer | adenocarcinoma | localized | tumor cells 43.5%, immune cells 69% | better | tumor cells expression - better DFS | [30] |
Tanaka K et al. | 180 | esophageal cancer | SCC | localized | 29.4% | worse | worse OS for patients after neoadjuvant chemotherapy | [31] |
Li Z et al. | 137 | gastric cancer | adenocarcinoma | all stages | 40.9% | worse | worse OS | [32] |
Wang L et al. | 550 | gastric cancer | adenocarcinoma | all stages | 37.3% | no impact | not associated | [33] |
Saito R et al. | 96 | gastric cancer | adenocarcinoma | not specified | tumor cells 34%, stromal cells 45% | worse | worse OS and DSS | [34] |
Cho J et al. | 78 | gastric cancer | adenocarcinoma | all stages | 9% tumor cells, 60.3% immune cells | better | better OS (immune cells PD-L1+) | [35] |
Ma C et al. | 44 | gastric cancer | adenocarcinoma | all stages | 72% | no impact | not associated | [36] |
Koh J et al. | 392 | gastric cancer | adenocarcinoma | II/III | 25% | no impact | not associated | [37] |
Author | Number of Patients | Type of Cancer | Histology | Disease Stage | Percentage of Positivity | Prognosis | Prognostic Value | Reference | |
---|---|---|---|---|---|---|---|---|---|
PD-1 | Chen K et al. | 349 | esophageal cancer | SCC | localized | 33.5% | no impact | no impact | [51] |
Wu Y et al. | 340 | gastric cancer | adenocarcinoma | all stages | 22.6% | better | improved OS | [52] | |
Böger C et al. | 465 | gastric cancer | adenocarcinoma | all stages | primary cancer 53.8%, liver metastases 73.3% | better | improved tumor specific survival | [12] | |
Eto S et al. | 105 | gastric cancer | adenocarcinoma | II/III | 26.7% | worse | worse DFS | [16] | |
Kollmann D et al. | 168 | esophageal cancer | adenocarcinoma | localized | tumor cells 77.4%, immune cells 81% | worse | worse OS and DFS | [30] | |
PD-L2 | Seo AN et al. | 116 | gastric cancer | adenocarcinoma | localized | tumor cells 21.6%, stromal cells 38.8% | no impact | not statistically significant trend towards-improved DFS | [27] |
Hsieh CC et al. | 150 | esophageal cancer | SCC | localized | 42% | no impact | no impact | [29] | |
Tanaka K et al. | 180 | esophageal cancer | SCC | localized | 48.3% | worse | worse OS for patients after neoadjuvant chemotherapy | [31] |
Author | Histology | Stage | Number of MSI-H Patients | MSI-H Frequency | Prognostic Role of MSI-H Phenotype | Prognostic/Predictive Value | Reference |
---|---|---|---|---|---|---|---|
Kim H et al. | adenocarcinoma | all stages | 161 | 9% | better | improved prognosis | [61] |
An JY et al. | adenocarcinoma | all stages | 170 | 8.5% | no impact | no benefit from adjuvant chemotherapy in MSI-H patients | [62] |
Fang WL et al. | adenocarcinoma | I–III | 25 | 11.7% | better | improved 5-year OS (68% vs. 47.6%, p = 0.030), trend towards better DFS at 3 years | [63] |
Beghelli S et al. | adenocarcinoma | all stages | 83 | 16% | better | improved survival in stage II patients | [64] |
Kim SY et al. | adenocarcinoma | II–III | 105 | 8.2% | better | improved prognosis without chemotherapy | [65] |
Smyth EC et al. | adenocarcinoma | localized | 20 | 8.5% | better | worse prognosis when treated with chemotherapy | [59] |
Polom K et al. | adenocarcinoma | metastatic | 14 | 8.0% | better | improved OS (15.9 vs. 8 months, p = 0.023) | [56] |
Giampieri R et al. | adenocarcinoma | metastatic | 15 | 14% | better | improved overall survival | [66] |
Corso G et al. | adenocarcinoma | all stages | 63 | 25.2% | better | improved long term survival | [57] |
Oki E et al. | adenocarcinoma | all stages | 22 | 9.4% | No prognostic role | No prognostic role | [67] |
Falchetti M et al. | adenocarcinoma | localized | 27 | 17% | better | improved survival (p = 0.1) | [68] |
Marrelli D et al. | adenocarcinoma | all stages | 111 | 23.5% | better | improved 5-year survival (67.6% vs. 35%, p < 0.001) | [69] |
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Vrána, D.; Matzenauer, M.; Neoral, Č.; Aujeský, R.; Vrba, R.; Melichar, B.; Rušarová, N.; Bartoušková, M.; Jankowski, J. From Tumor Immunology to Immunotherapy in Gastric and Esophageal Cancer. Int. J. Mol. Sci. 2019, 20, 13. https://doi.org/10.3390/ijms20010013
Vrána D, Matzenauer M, Neoral Č, Aujeský R, Vrba R, Melichar B, Rušarová N, Bartoušková M, Jankowski J. From Tumor Immunology to Immunotherapy in Gastric and Esophageal Cancer. International Journal of Molecular Sciences. 2019; 20(1):13. https://doi.org/10.3390/ijms20010013
Chicago/Turabian StyleVrána, David, Marcel Matzenauer, Čestmír Neoral, René Aujeský, Radek Vrba, Bohuslav Melichar, Nikol Rušarová, Marie Bartoušková, and Janusz Jankowski. 2019. "From Tumor Immunology to Immunotherapy in Gastric and Esophageal Cancer" International Journal of Molecular Sciences 20, no. 1: 13. https://doi.org/10.3390/ijms20010013
APA StyleVrána, D., Matzenauer, M., Neoral, Č., Aujeský, R., Vrba, R., Melichar, B., Rušarová, N., Bartoušková, M., & Jankowski, J. (2019). From Tumor Immunology to Immunotherapy in Gastric and Esophageal Cancer. International Journal of Molecular Sciences, 20(1), 13. https://doi.org/10.3390/ijms20010013