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Expression of PD-L1...
Expression of PD-L1 and PD-1 in chemoradiotherapy-Naïve esophageal and gastric adenocarcinoma : Relationship with mismatch repair status and survival
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- Svensson, Maria C. (author)
- Lund University,Lunds universitet,Personlig patologi och cancerbehandling,Forskargrupper vid Lunds universitet,Personalized Pathology & Cancer Therapy,Lund University Research Groups
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- Borg, David (author)
- Lund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine
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- Zhang, Cheng (author)
- KTH,KTH Royal Institute of Technology,Science for Life Laboratory, SciLifeLab
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- Hedner, Charlotta (author)
- Lund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine
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- Nodin, Björn (author)
- Lund University,Lunds universitet,Personlig patologi och cancerbehandling,Forskargrupper vid Lunds universitet,Personalized Pathology & Cancer Therapy,Lund University Research Groups
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- Uhlén, Mathias (author)
- KTH,KTH Royal Institute of Technology,Science for Life Laboratory, SciLifeLab
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- Mardinoglu, Adil (author)
- KTH,KTH Royal Institute of Technology,King's College London,Science for Life Laboratory, SciLifeLab
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- Leandersson, Karin (author)
- Lund University,Lunds universitet,Cancerimmunologi, Malmö,Forskargrupper vid Lunds universitet,Cancer Immunology, Malmö,Lund University Research Groups
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- Jirström, Karin (author)
- Lund University,Lunds universitet,Personlig patologi och cancerbehandling,Forskargrupper vid Lunds universitet,Personalized Pathology & Cancer Therapy,Lund University Research Groups
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(creator_code:org_t)
- 2019-03-13
- 2019
- English.
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In: Frontiers in Oncology. - : Frontiers Media SA. - 2234-943X. ; 9:MAR
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https://www.frontier...
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https://doi.org/10.3...
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https://kth.diva-por... (primary) (Raw object)
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https://lup.lub.lu.s...
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https://doi.org/10.3...
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https://urn.kb.se/re...
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Abstract
Subject headings
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Keyword
- Esophageal cancer
- Gastric cancer
- MMR status
- MSI status
- PD-1
- PD-L1
- The cancer genome atlas
Publication and Content Type
- art (subject category)
- ref (subject category)
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