Prognostic significance of lymphocyte-activation gene-3 expression in chemoradiotherapy-naïve esophageal and gastric adenocarcinoma
(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)
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https://lup.lub.lu.se/record/d05e69ee-9af9-44da-95b6-ac862c5f6f09
- author
- Siesing, C. LU ; Svensson, M. C. LU ; Hedner, C. LU ; Nodin, B. LU ; Borg, D. LU and Jirstrom, K. LU
- organization
- publishing date
- 2018
- 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 (>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}}, }