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Expression of PD-L1 and PD-1 in chemoradiotherapy-Naïve esophageal and gastric adenocarcinoma : Relationship with mismatch repair status and survival

Svensson, Maria C. LU ; Borg, David LU ; Zhang, Cheng ; Hedner, Charlotta LU ; Nodin, Björn LU ; Uhlén, Mathias ; Mardinoglu, Adil ; Leandersson, Karin LU and Jirström, Karin LU (2019) In Frontiers in Oncology 9(MAR).
Abstract


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... (More)


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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author
; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Esophageal cancer, Gastric cancer, MMR status, MSI status, PD-1, PD-L1, The cancer genome atlas
in
Frontiers in Oncology
volume
9
issue
MAR
article number
136
publisher
Frontiers Media S. A.
external identifiers
  • scopus:85063302688
  • pmid:30931254
ISSN
2234-943X
DOI
10.3389/fonc.2019.00136
language
English
LU publication?
yes
id
bcfb9ab2-72d9-4213-9d80-4f4d26a4487b
date added to LUP
2019-04-02 12:47:25
date last changed
2022-08-03 03:04:17
@article{bcfb9ab2-72d9-4213-9d80-4f4d26a4487b,
  abstract     = {{<p><br>
                                                         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                             <br>
                            <sup>+</sup><br>
                                                          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.                         <br>
                        </p>}},
  author       = {{Svensson, Maria C. and Borg, David and Zhang, Cheng and Hedner, Charlotta and Nodin, Björn and Uhlén, Mathias and Mardinoglu, Adil and Leandersson, Karin and Jirström, Karin}},
  issn         = {{2234-943X}},
  keywords     = {{Esophageal cancer; Gastric cancer; MMR status; MSI status; PD-1; PD-L1; The cancer genome atlas}},
  language     = {{eng}},
  month        = {{03}},
  number       = {{MAR}},
  publisher    = {{Frontiers Media S. A.}},
  series       = {{Frontiers in Oncology}},
  title        = {{Expression of PD-L1 and PD-1 in chemoradiotherapy-Naïve esophageal and gastric adenocarcinoma : Relationship with mismatch repair status and survival}},
  url          = {{http://dx.doi.org/10.3389/fonc.2019.00136}},
  doi          = {{10.3389/fonc.2019.00136}},
  volume       = {{9}},
  year         = {{2019}},
}