Prognostic value and clinicopathological roles of the tumor immune microenvironment in salivary duct carcinoma.
Immune microenvironment
PD-L1
Prognosis
Salivary duct carcinoma
Salivary gland tumor
Journal
Virchows Archiv : an international journal of pathology
ISSN: 1432-2307
Titre abrégé: Virchows Arch
Pays: Germany
ID NLM: 9423843
Informations de publication
Date de publication:
Sep 2023
Sep 2023
Historique:
received:
21
05
2023
accepted:
07
07
2023
revised:
21
06
2023
medline:
23
10
2023
pubmed:
19
7
2023
entrez:
18
7
2023
Statut:
ppublish
Résumé
Salivary duct carcinoma (SDC) is an aggressive type of salivary gland carcinoma. Recently, immunotherapies targeting immune checkpoints, including PD1, PD-L1, CTLA4, and LAG3, have had a considerable prognostic impact on various malignant tumors. The implementation of such immune checkpoint inhibitor (ICI) therapies has also been attempted in cases of salivary gland carcinoma. The tumor immune microenvironment (TIME) is implicated in tumorigenesis and tumor progression and is closely associated with the response to ICI therapies. However, the TIME in SDC has not been fully explored. We examined the immunohistochemical expression of CD8, FOXP3, PD1, PD-L1, CTLA4, LAG3, and mismatch repair (MMR) proteins, tumor-infiltrating lymphocytes (TILs), and microsatellite instability (MSI) status in 175 cases of SDC. The associations between these TIME-related markers and the clinicopathological factors and prognosis were evaluated. An elevated expression of CD8, FOXP3, PD1, CTLA4, and LAG3 was associated with more aggressive histological features and an advanced N and/or M classification, elevated Ki-67 index, and poor prognosis. Furthermore, cases with a high PD-L1 expression exhibited more aggressive histological features and adverse clinical outcomes than those with a low expression. Alternatively, there was no significant correlation between TILs and clinicopathological factors. No SDC cases with an MSI-high status or MMR deficiency were found. The coexistence of both an immunostimulatory and immunosuppressive TIME in aggressive SDC might play a role in the presence of T-cell exhaustion. The contribution of multiple immune escape pathways, including regulatory T cells and immune checkpoints, may provide a rationale for ICI therapy, including combined PD1/CTLA4 blockade therapy.
Identifiants
pubmed: 37464232
doi: 10.1007/s00428-023-03598-3
pii: 10.1007/s00428-023-03598-3
doi:
Substances chimiques
B7-H1 Antigen
0
CTLA-4 Antigen
0
Forkhead Transcription Factors
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
367-379Subventions
Organisme : Japan Society for the Promotion of Science
ID : 21K09616
Organisme : Japan Society for the Promotion of Science
ID : 20K07417
Organisme : Japan Society for the Promotion of Science
ID : 23K06432
Organisme : Japan Society for the Promotion of Science
ID : 20K07597
Organisme : Japan Society for the Promotion of Science
ID : 22K06939
Organisme : Japan Society for the Promotion of Science
ID : 19K165681
Organisme : Japan Society for the Promotion of Science
ID : 22K06969
Organisme : Japan Society for the Promotion of Science
ID : 21K16835
Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
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