Research output: Contribution to journal › Article › peer-review
Maria C Svensson, David Borg, Cheng Zhang, Charlotta Hedner, Björn Nodin, Mathias Uhlén, Adil Mardinoglu, Karin Leandersson, Karin Jirström
Original language | English |
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Article number | 136 |
Pages (from-to) | 136 |
Journal | Frontiers in oncology |
Volume | 9 |
Issue number | MAR |
DOIs | |
Accepted/In press | 15 Feb 2019 |
Published | 13 Mar 2019 |
Additional links |
Expression of PD-L1 and PD-1_SCENSSON_Accepted14February2019_GOLD VoR
fonc_09_00136.pdf, 4.29 MB, application/pdf
Uploaded date:09 May 2019
Version:Final published version
Licence:CC BY
Background: The outlook for patients with esophageal and gastric (EG) cancer remains poor. Hence, there is a compelling need to identify novel treatment strategies and complementary biomarkers. Programmed death ligand 1 (PD-L1) and mismatch repair deficiency (dMMR) are putative biomarkers of response to immune-checkpoint blockade, but their prognostic value and interrelationship in EG cancer have been sparsely investigated. Methods: Immunohistochemical expression of PD-L1 on tumour cells (TC) and tumour-infiltrating immune cells (TIC), and of PD-1 (programmed death receptor 1) on TIC was assessed using tissue microarrays with primary tumours and a subset of paired lymph node metastases from a consecutive, retrospective cohort of 174 patients with chemoradiotherapy-naïve EG adenocarcinoma. MMR proteins MLH1, PMS2, MSH2, and MSH6 were assessed by immunohistochemistry. The total number (intratumoural, tumour-adjacent, and stromal) of CD8+ T cells in each core was calculated by automated analysis. Results: High PD-L1 expression on both TC and TIC, but not PD-1 expression, was significantly associated with dMMR. PD-L1 expression on TIC was significantly higher in lymph node metastases than in primary tumours. High expression of PD-L1 or PD-1 on TIC was significantly associated with a prolonged survival, the former independently of established prognostic factors. A significant stepwise positive association was found between CD8+ T cells and categories of PD-L1 expression on TIC. Conclusion: PD-L1 expression on TIC is higher in lymph node metastases compared to primary tumours, correlates with dMMR, and is an independent factor of prolonged survival in patients with chemoradiotherapy-naïve EG adenocarcinoma. These findings suggest that PD-L1 expression on TIC may be a useful biomarker for identifying patients who may not need additional chemo- or chemoradiotherapy, and who may benefit from PD-1/PD-L1 immune-checkpoint blockade.
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