Prognostic significance of immune checkpoints in the tumour-stromal microenvironment of sebaceous gland carcinoma.
Adenocarcinoma, Sebaceous
/ metabolism
Adult
Aged
Aged, 80 and over
B7-H1 Antigen
/ genetics
Blotting, Western
CD4 Antigens
/ metabolism
CD8 Antigens
/ metabolism
CTLA-4 Antigen
/ genetics
Eyelid Neoplasms
/ metabolism
Female
Humans
Immune Checkpoint Proteins
/ genetics
Immunohistochemistry
Kaplan-Meier Estimate
Male
Middle Aged
Prognosis
Programmed Cell Death 1 Receptor
/ genetics
Proportional Hazards Models
RNA, Messenger
/ genetics
Real-Time Polymerase Chain Reaction
Sebaceous Gland Neoplasms
/ metabolism
Stromal Cells
/ metabolism
Tumor Microenvironment
/ physiology
eye lids
immunology
pathology
Journal
The British journal of ophthalmology
ISSN: 1468-2079
Titre abrégé: Br J Ophthalmol
Pays: England
ID NLM: 0421041
Informations de publication
Date de publication:
01 2021
01 2021
Historique:
received:
30
10
2019
revised:
02
03
2020
accepted:
11
03
2020
pubmed:
12
4
2020
medline:
24
4
2021
entrez:
12
4
2020
Statut:
ppublish
Résumé
Immune checkpoint blockade strategies have gained attention in the treatment/prognosis of cancers by targeting the programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) pathway alone or in combination with cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) blockade and are currently in clinical trials. The present study investigated the expression of the PD-1, PD-L1, CTLA-4, CD4 and CD8 proteins and their prognostic value in the tumour microenvironment of sebaceous gland carcinoma (SGC). The expression levels of PD-1, PD-L1, CTLA-4, CD4 and CD8 proteins were assessed in 52 cases of SGC by immunohistochemistry and validated by western blotting. mRNA expression was measured by quantitative real-time PCR. Kaplan-Meier curves and Cox proportional hazard models were used to analyse the correlation of protein expression with clinicopathological parameters and disease-free survival. The expression of PD-L1 was found to be higher in tumour cells than in stromal cells. In univariate analysis, the expression of PD-1 in tumour-infiltrating lymphocytes (tPD-1) and PD-L1 in tumour cells was associated with reduced disease-free survival, whereas PD-L1 expression in stromal lymphocyte infiltration (sPD-L1) was associated with the increased survival of patients (p<0.05). However, by multivariate analysis, the expression of tPD-1 was found to be an independent prognostic factor for poor survival. Our study highlights the prognostic outcome of PD-1 and PD-L1 protein expression in cells of tumour-stromal compartments. These results indicate that the PD-1/PD-L1 pathway mediates important interactions within the tumour microenvironment in SGC.
Sections du résumé
BACKGROUND
Immune checkpoint blockade strategies have gained attention in the treatment/prognosis of cancers by targeting the programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) pathway alone or in combination with cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) blockade and are currently in clinical trials. The present study investigated the expression of the PD-1, PD-L1, CTLA-4, CD4 and CD8 proteins and their prognostic value in the tumour microenvironment of sebaceous gland carcinoma (SGC).
METHODS
The expression levels of PD-1, PD-L1, CTLA-4, CD4 and CD8 proteins were assessed in 52 cases of SGC by immunohistochemistry and validated by western blotting. mRNA expression was measured by quantitative real-time PCR. Kaplan-Meier curves and Cox proportional hazard models were used to analyse the correlation of protein expression with clinicopathological parameters and disease-free survival.
RESULTS
The expression of PD-L1 was found to be higher in tumour cells than in stromal cells. In univariate analysis, the expression of PD-1 in tumour-infiltrating lymphocytes (tPD-1) and PD-L1 in tumour cells was associated with reduced disease-free survival, whereas PD-L1 expression in stromal lymphocyte infiltration (sPD-L1) was associated with the increased survival of patients (p<0.05). However, by multivariate analysis, the expression of tPD-1 was found to be an independent prognostic factor for poor survival.
CONCLUSION
Our study highlights the prognostic outcome of PD-1 and PD-L1 protein expression in cells of tumour-stromal compartments. These results indicate that the PD-1/PD-L1 pathway mediates important interactions within the tumour microenvironment in SGC.
Identifiants
pubmed: 32277010
pii: bjophthalmol-2019-315490
doi: 10.1136/bjophthalmol-2019-315490
doi:
Substances chimiques
B7-H1 Antigen
0
CD274 protein, human
0
CD4 Antigens
0
CD8 Antigens
0
CTLA-4 Antigen
0
CTLA4 protein, human
0
Immune Checkpoint Proteins
0
PDCD1 protein, human
0
Programmed Cell Death 1 Receptor
0
RNA, Messenger
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
48-56Informations de copyright
© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.
Déclaration de conflit d'intérêts
Competing interests: None declared.