Article Text

Download PDFPDF

193 PD-L1 expression in gastroesophageal cancer: A systematic literature review
  1. Zev A Wainberg1,
  2. Sasan Jahanian2 and
  3. Michelle Sidel3
  1. 1University of California, Los Angeles, CA, USA
  2. 2Thomas Jefferson University, Philadelphia, PA, USA
  3. 3Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA


Background It is well established that many gastroesophageal (GE) cancers are immune-sensitive. Programmed death ligand-1 (PD-L1) expression may have a predictive value in GE cancers. PD-L1/PD-1 inhibitors have profoundly influenced the cancer treatment landscape in recent years. Assessing PD-L1 levels before and after treatment may help in making appropriate treatment decisions. The purpose of this systematic review was to assess the clinical evidence and impact of various treatment interventions on the dynamics of PD-L1 expression in GE cancers.

Methods A literature search was performed on Medline, Embase,, and trialtrove using relevant search terms related to PD-L1 and upper GE cancers (Jan 1996-Sep 2022). Two independent reviewers screened and included full-text English articles, while excluding preclinical studies and case reports.

Results Of the 206 articles screened, 38 publications (21 reviews/meta-analyses; 17 research studies) were identified and critically reviewed. PD-L1 is expressed in approximately 30%-65% of tumors in patients with gastric cancers; expression of PD-L1 is positively correlated to the depth of invasion, metastasis, tumor size, and progression.1 PD-L1 levels were also increased in the peripheral blood of patients with gastric cancers.2 3 Higher PD-L1 expression was seen in GE cancers with microsatellite instability and Epstein-Barr virus positivity.4 5 A positive correlation was noted between FOXP3, MLH1, HLA Class I, CD3+/CD8+ T cells expression and PD-L1 levels.1 6 7 PD-L1 expression has been associated with worse prognosis and shorter survival in GE cancers (hazard ratio range: 1.42–1.74).6 8–13 Enhanced responses to immunotherapy have been observed in patients with greater PD-L1 combined positive score (CPS) in GE cancers.1 4 14–17 The pre- and post-treatment PD-L1 levels in GE cancers have been found to differ, with increased levels observed after targeted therapy, chemotherapy, or radiation, although this finding is inconsistent across studies.15 18 19

Conclusions There is a need for standardization of PD-L1 testing recommendations. PD-L1 expression has been associated with poor prognosis and is routinely evaluated before first-line treatment, but there is limited information on the impact of initiated therapy on post-treatment PD-L1 levels. This review suggests that PD-L1 levels may change in response to chemotherapy or radiation, thereby identifying patients suitable for immunotherapy, upon progression. Evaluating PD-L1 levels before initiating second-line therapy is important to ensure the most effective treatment choices.

Acknowledgements The authors received medical writing support for this abstract from Indumathy Pinnamaneni (Novartis Healthcare Pvt. Ltd., Hyderabad, India).


  1. Lin E, Gong J, Klempner SJ, Chao J. Advances in immuno-oncology biomarkers for gastroesophageal cancer: Programmed death ligand 1, microsatellite instability, and beyond. World Journal of Gastroenterology. 2018;24:2686–2697.

  2. Amatatsu M, Arigami T, Uenosono Y, et al. Programmed death-ligand 1 is a promising blood marker for predicting tumor progression and prognosis in patients with gastric cancer. Cancer Sci. 2018;109(3):814–820.

  3. Liu YX, Wang XS, Wang YF, et al. Prognostic significance of PD-L1 expression in patients with gastric cancer in East Asia: a meta-analysis. Onco Targets Ther. 2016;9:2649–2654.

  4. Chang X, Ge X, Zhang Y, Xue X. The current management and biomarkers of immunotherapy in advanced gastric cancer. Medicine (Baltimore). 2022;101(21):e29304.

  5. Choi E, Chang MS, Byeon S-J, et al. Prognostic perspectives of PD-L1 combined with tumor-infiltrating lymphocytes, Epstein-Barr virus, and microsatellite instability in gastric carcinomas. Diagnostic Pathology. 2020;15(1):69.

  6. Yu W, Guo Y. Prognostic significance of programmed death ligand-1 immunohistochemical expression in esophageal cancer: A meta-analysis of the literature. Medicine (Baltimore). 2018;97(30):e11614.

  7. Wang Y, Zhu C, Song W, Li J, Zhao G, Cao H. PD-L1 Expression and CD8(+) T Cell Infiltration Predict a Favorable Prognosis in Advanced Gastric Cancer. J Immunol Res. 2018;2018:4180517.

  8. Wu P, Wu D, Li L, Chai Y, Huang J. PD-L1 and Survival in Solid Tumors: A Meta-Analysis. PLoS One. 2015;10(6):e0131403.

  9. Xu F, Feng G, Zhao H, et al. Clinicopathologic Significance and Prognostic Value of B7 Homolog 1 in Gastric Cancer: A Systematic Review and Meta-Analysis. Medicine (Baltimore). 2015;94(43):e1911.

  10. Zhang M, Dong Y, Liu H, et al. The clinicopathological and prognostic significance of PD-L1 expression in gastric cancer: a meta-analysis of 10 studies with 1,901 patients. Sci Rep. 2016;6:37933.

  11. Pyo JS, Kang G, Kim JY. Prognostic role of PD-L1 in malignant solid tumors: a meta-analysis. Int J Biol Markers. 2017;32(1):e68-e74.

  12. Dai C, Wang M, Lu J, et al. Prognostic and predictive values of PD-L1 expression in patients with digestive system cancer: a meta-analysis. Onco Targets Ther. 2017;10:3625–3634.

  13. Yagi T, Baba Y, Ishimoto T, et al. PD-L1 Expression, Tumor-infiltrating Lymphocytes, and Clinical Outcome in Patients With Surgically Resected Esophageal Cancer. Ann Surg. 2019;269(3):471–478.

  14. Wylie LA, Baker HC, Smyth EC. Mind the target: programmed death ligand 1 in oesophagogastric cancers. Current Opinion in Oncology. 2022;34(4):389–394.

  15. Soeratram TT, Creemers A, Meijer SL, et al. Tumor-immune landscape patterns before and after chemoradiation in resectable esophageal adenocarcinomas. J Pathol. 2022;256(3):282–296.

  16. Kojima T, Shah MA, Muro K, et al. Randomized Phase III KEYNOTE-181 Study of Pembrolizumab Versus Chemotherapy in Advanced Esophageal Cancer. J Clin Oncol. 2020;38(35):4138–4148.

  17. Vivaldi C, Catanese S, Massa V, et al. Immune Checkpoint Inhibitors in Esophageal Cancers: Are We Finally Finding the Right Path in the Mist? International Journal of Molecular Sciences. 2020;21(5):1658.

  18. Kelly RJ. Emerging Multimodality Approaches to Treat Localized Esophageal Cancer. J Natl Compr Canc Netw. 2019;17(8):1009–1014.

  19. Tada Y, Togashi Y, Kotani D, et al. Targeting VEGFR2 with Ramucirumab strongly impacts effector/activated regulatory T cells and CD8+ T cells in the tumor microenvironment. Journal for ImmunoTherapy of Cancer. 2018;6(1):106.

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.