Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Prognostic significance of lymphocyte-activation gene-3 expression in chemoradiotherapy-naïve esophageal and gastric adenocarcinoma

Siesing, C. LU ; Svensson, M. C. LU ; Hedner, C. LU ; Nodin, B. LU ; Borg, D. LU and Jirstrom, K. LU orcid (2018) In Annals of oncology : official journal of the European Society for Medical Oncology 29(Suppl. 8). p.220-220
Abstract
Background: Neoadjuvant and/or adjuvant treatment has led to an improved survival in patients with resectable gastroesophageal adenocarcinoma (GEAC). Nevertheless, survival rates remain poor and, hence, there is a great need to identify novel treatment strategies and relevant complementary diagnostics. Immunotherapies targeting the PD‐1/PD‐L1 checkpoints have shown promising results, but simultaneous inhibition of other fundamental checkpoints, such as lymphocyte-activation gene-3 (LAG‐3), may further improve clinical outcome. The expression and prognostic significance of LAG-3 in GEAC has however not yet been described. Herein, we examined the expression of LAG-3 in tumour-infiltrating immune cells (TIC) in chemoradiotherapy-naïve GEAC... (More)
Background: Neoadjuvant and/or adjuvant treatment has led to an improved survival in patients with resectable gastroesophageal adenocarcinoma (GEAC). Nevertheless, survival rates remain poor and, hence, there is a great need to identify novel treatment strategies and relevant complementary diagnostics. Immunotherapies targeting the PD‐1/PD‐L1 checkpoints have shown promising results, but simultaneous inhibition of other fundamental checkpoints, such as lymphocyte-activation gene-3 (LAG‐3), may further improve clinical outcome. The expression and prognostic significance of LAG-3 in GEAC has however not yet been described. Herein, we examined the expression of LAG-3 in tumour-infiltrating immune cells (TIC) in chemoradiotherapy-naïve GEAC and paired lymph node metastases, with particular reference to its relationship with PD-1 and PD-L1 expression, mismatch repair (MMR) status, and survival.

Methods: Immunohistochemical LAG-3 expression was analysed in tissue microarrays with 165 primary tumours and 72 paired lymph node metastases from a retrospective consecutive cohort of patients with chemoradiotherapy-naïve resected GEAC. LAG-3 expression was denoted in categories of negative (0), low (1-10) and high (>10). PD-1, PD-L1 expression and MMR status had been previously analysed.

Results: The distribution of LAG-3 expression in primary tumours was 55.8% negative, 28.5% low, and 15.8% high. The corresponding figures in lymph node metastases were 48.6% negative, 37.5% low, and 13.9% high. LAG-3 expression did not differ by tumour location. Positive LAG-3 expression in primary tumours was an independent factor for prolonged overall survival in the entire cohort (HR = 0.64, 95% CI 0.43-0.96), and in gastric cancer (HR = 0.35, 95% CI 0.17-0.74). LAG-3 expression in primary tumours was significantly associated with PD-L1 expression in both tumour cells and TIC, and with PD-1 expression in TIC, but not with MMR status.

Conclusions: LAG-3 is expressed in a considerable proportion of GEAC, with a similar distribution in primary tumours and lymph node metastases. Positive LAG-3 expression is an independent favourable prognostic factor, particularly in gastric cancer. (Less)
Please use this url to cite or link to this publication:
author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Annals of oncology : official journal of the European Society for Medical Oncology
volume
29
issue
Suppl. 8
pages
220 - 220
publisher
Oxford University Press
external identifiers
  • pmid:32136473
ISSN
1569-8041
DOI
10.1093/annonc/mdy282.039
language
English
LU publication?
yes
id
d05e69ee-9af9-44da-95b6-ac862c5f6f09
date added to LUP
2020-03-31 13:34:13
date last changed
2024-01-29 02:51:59
@misc{d05e69ee-9af9-44da-95b6-ac862c5f6f09,
  abstract     = {{Background: Neoadjuvant and/or adjuvant treatment has led to an improved survival in patients with resectable gastroesophageal adenocarcinoma (GEAC). Nevertheless, survival rates remain poor and, hence, there is a great need to identify novel treatment strategies and relevant complementary diagnostics. Immunotherapies targeting the PD‐1/PD‐L1 checkpoints have shown promising results, but simultaneous inhibition of other fundamental checkpoints, such as lymphocyte-activation gene-3 (LAG‐3), may further improve clinical outcome. The expression and prognostic significance of LAG-3 in GEAC has however not yet been described. Herein, we examined the expression of LAG-3 in tumour-infiltrating immune cells (TIC) in chemoradiotherapy-naïve GEAC and paired lymph node metastases, with particular reference to its relationship with PD-1 and PD-L1 expression, mismatch repair (MMR) status, and survival.<br>
<br>
Methods: Immunohistochemical LAG-3 expression was analysed in tissue microarrays with 165 primary tumours and 72 paired lymph node metastases from a retrospective consecutive cohort of patients with chemoradiotherapy-naïve resected GEAC. LAG-3 expression was denoted in categories of negative (0), low (1-10) and high (&gt;10). PD-1, PD-L1 expression and MMR status had been previously analysed.<br>
<br>
Results: The distribution of LAG-3 expression in primary tumours was 55.8% negative, 28.5% low, and 15.8% high. The corresponding figures in lymph node metastases were 48.6% negative, 37.5% low, and 13.9% high. LAG-3 expression did not differ by tumour location. Positive LAG-3 expression in primary tumours was an independent factor for prolonged overall survival in the entire cohort (HR = 0.64, 95% CI 0.43-0.96), and in gastric cancer (HR = 0.35, 95% CI 0.17-0.74). LAG-3 expression in primary tumours was significantly associated with PD-L1 expression in both tumour cells and TIC, and with PD-1 expression in TIC, but not with MMR status.<br>
<br>
Conclusions: LAG-3 is expressed in a considerable proportion of GEAC, with a similar distribution in primary tumours and lymph node metastases. Positive LAG-3 expression is an independent favourable prognostic factor, particularly in gastric cancer.}},
  author       = {{Siesing, C. and Svensson, M. C. and Hedner, C. and Nodin, B. and Borg, D. and Jirstrom, K.}},
  issn         = {{1569-8041}},
  language     = {{eng}},
  note         = {{Conference Abstract}},
  number       = {{Suppl. 8}},
  pages        = {{220--220}},
  publisher    = {{Oxford University Press}},
  series       = {{Annals of oncology : official journal of the European Society for Medical Oncology}},
  title        = {{Prognostic significance of lymphocyte-activation gene-3 expression in chemoradiotherapy-naïve esophageal and gastric adenocarcinoma}},
  url          = {{http://dx.doi.org/10.1093/annonc/mdy282.039}},
  doi          = {{10.1093/annonc/mdy282.039}},
  volume       = {{29}},
  year         = {{2018}},
}