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)
(Less)
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.
- author
- 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
- organization
- publishing date
- 2019-03-13
- 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
-
- pmid:30931254
- scopus:85063302688
- 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
- 2024-07-23 12:14:38
@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}},
}