Prognostic significance of PD-1/PD-L1 expression in uveal melanoma: correlation with tumor-infiltrating lymphocytes and clinicopathological parameters.
B7-H1 Antigen
/ genetics
Cell Line, Tumor
Cell Movement
Eye Neoplasms
/ diagnosis
Follow-Up Studies
Humans
Immunohistochemistry
Immunotherapy
/ methods
Interferon-gamma
/ metabolism
Lymphocytes, Tumor-Infiltrating
/ immunology
Melanoma
/ diagnosis
Polymerase Chain Reaction
Prognosis
Programmed Cell Death 1 Receptor
/ genetics
Survival Analysis
Uveal Neoplasms
/ diagnosis
Immunotherapy
Interferon gamma
Tumor-infiltrating lymphocytes
Uveal melanoma
Journal
Cancer immunology, immunotherapy : CII
ISSN: 1432-0851
Titre abrégé: Cancer Immunol Immunother
Pays: Germany
ID NLM: 8605732
Informations de publication
Date de publication:
May 2021
May 2021
Historique:
received:
08
05
2020
accepted:
19
10
2020
pubmed:
3
11
2020
medline:
5
5
2021
entrez:
2
11
2020
Statut:
ppublish
Résumé
To understand how to improve the effect of immune checkpoint inhibitors in uveal melanoma (UM), we need a better understanding of the expression of PD-1 and PD-L1, their relation with the presence of tumor-infiltrating lymphocytes (TILs), and their prognostic relevance in UM patients. Expression of PD-1 and PD-L1 was assessed in 71 UM tissue samples by immunohistochemistry and quantitative real-time PCR (qRT-PCR), and further validated by western blotting. The effect of interferon gamma (IFN-γ) on PD-1/PD-L1 expression was determined on four UM cell lines. Immunoreactivity of PD-1 was found in 30/71 cases and of PD-L1 in 44/71 UM samples. Tumor-infiltrating lymphocytes were found in 46% of UM tissues. PD-1 was expressed on TILs while tumor cells expressed PD-L1. UM with and without TILs showed expression of PD-1 in 69% and 18% cases, respectively (p = 0.001). Similarly, PD-L1 was found in 75% of UM with TILs and in 50% of cases without TILs, respectively (p = 0.03). DFS rate were lower in patients with TILs with expression of PD-1 and PD-L1, but the rate of DFS was higher with expression of PD-L1 in patients without TILs. After treatment of UM cell lines with IFN-γ, PD-1 expression was induced in all UM cell lines whereas PD-L1 expression was found at a lower level in untreated cells, while expression also increased following treatment with IFN-γ. Our study suggests that increased infiltration with TILs promotes the aggressive behavior and suppresses the immune response of UM cells, thereby inhibiting immunotherapy.
Sections du résumé
BACKGROUND
BACKGROUND
To understand how to improve the effect of immune checkpoint inhibitors in uveal melanoma (UM), we need a better understanding of the expression of PD-1 and PD-L1, their relation with the presence of tumor-infiltrating lymphocytes (TILs), and their prognostic relevance in UM patients.
MATERIALS AND METHODS
METHODS
Expression of PD-1 and PD-L1 was assessed in 71 UM tissue samples by immunohistochemistry and quantitative real-time PCR (qRT-PCR), and further validated by western blotting. The effect of interferon gamma (IFN-γ) on PD-1/PD-L1 expression was determined on four UM cell lines.
RESULTS
RESULTS
Immunoreactivity of PD-1 was found in 30/71 cases and of PD-L1 in 44/71 UM samples. Tumor-infiltrating lymphocytes were found in 46% of UM tissues. PD-1 was expressed on TILs while tumor cells expressed PD-L1. UM with and without TILs showed expression of PD-1 in 69% and 18% cases, respectively (p = 0.001). Similarly, PD-L1 was found in 75% of UM with TILs and in 50% of cases without TILs, respectively (p = 0.03). DFS rate were lower in patients with TILs with expression of PD-1 and PD-L1, but the rate of DFS was higher with expression of PD-L1 in patients without TILs. After treatment of UM cell lines with IFN-γ, PD-1 expression was induced in all UM cell lines whereas PD-L1 expression was found at a lower level in untreated cells, while expression also increased following treatment with IFN-γ.
CONCLUSION
CONCLUSIONS
Our study suggests that increased infiltration with TILs promotes the aggressive behavior and suppresses the immune response of UM cells, thereby inhibiting immunotherapy.
Identifiants
pubmed: 33136179
doi: 10.1007/s00262-020-02773-8
pii: 10.1007/s00262-020-02773-8
doi:
Substances chimiques
B7-H1 Antigen
0
Programmed Cell Death 1 Receptor
0
Interferon-gamma
82115-62-6
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1291-1303Subventions
Organisme : Science and Engineering Research Board
ID : NPDF/2016/000903
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