Clinical prognosticators and targets in the immune microenvironment of intrahepatic cholangiocarcinoma.
Humans
Cholangiocarcinoma
/ immunology
Tumor Microenvironment
/ immunology
Male
Female
Bile Duct Neoplasms
/ immunology
Middle Aged
Prognosis
Aged
Biomarkers, Tumor
/ metabolism
B7-H1 Antigen
/ metabolism
STAT1 Transcription Factor
/ metabolism
Lymphocytes, Tumor-Infiltrating
/ immunology
Antigens, CD
/ metabolism
Adult
CD4-Positive T-Lymphocytes
/ immunology
Antigens, Differentiation, Myelomonocytic
/ metabolism
CD68 Molecule
Immune cell prognosticators
immunomodulation
intrahepatic cholangiocarcinoma
tumor immune microenvironment
Journal
Oncoimmunology
ISSN: 2162-402X
Titre abrégé: Oncoimmunology
Pays: United States
ID NLM: 101570526
Informations de publication
Date de publication:
2024
2024
Historique:
medline:
3
10
2024
pubmed:
3
10
2024
entrez:
3
10
2024
Statut:
epublish
Résumé
Intrahepatic cholangiocarcinoma (ICC) is a disease with poor prognosis and limited therapeutic options. We investigated the tumor immune microenvironment (TIME) to identify predictors of disease outcome and to explore targets for therapeutic modulation. Liver tissue samples were collected during 2008-2019 from patients ( CD68+ cells were the predominant immune cell type in the TIME of ICC. CD4+ These results highlight the importance of CD4+ T cells in immune response against ICC. Secondly, a subset of tumors with "hot" TIME represents potential candidates for ICI, while stimulation of STAT1 pathway could be a potential target to turn "cold" into "hot" TIME in ICC. The tumor immune microenvironment (TIME) plays a critical role in the immune response In many cancers, including intrahepatic cholangiocarcinoma (ICC). Molecular subtyping of the ICC microenvironment already revealed inter-tumoral heterogeneity with variant profiles of immune cell infiltrates. A recent study created an in-depth immune cell atlas of the TIME in biliary tract cancers and could demonstrate the relevance of specific immune cell subpopulations on patient outcome. We are able to provide a distinctive characterization of TIME, separating tumor epithelial- and stroma areas, in a large and representative ICC cohort using digitalized image analysis on tissue microarrays (TMA) as well as multiplex imaging mass cytometry (IMC). The study was designed for identification of immune cell prognosticators allocating institutional ICC patients into a discovery (2008–15) and a validation (2010–19) cohort. Immune cell subpopulations were correlated with clinicopathological characteristics and patient outcome. Our results highlight: i. The important role of CD4+ T cell infiltration in ICC patients; ii. ICC tumors with high density of immune cells associated with PD-L1 expression identifies a subset of patients with variant tumor biology; iii. Stimulation of STAT1 pathway may be a relevant target to turn “
Sections du résumé
Background
UNASSIGNED
Intrahepatic cholangiocarcinoma (ICC) is a disease with poor prognosis and limited therapeutic options. We investigated the tumor immune microenvironment (TIME) to identify predictors of disease outcome and to explore targets for therapeutic modulation.
Methods
UNASSIGNED
Liver tissue samples were collected during 2008-2019 from patients (
Results
UNASSIGNED
CD68+ cells were the predominant immune cell type in the TIME of ICC. CD4+
Conclusions
UNASSIGNED
These results highlight the importance of CD4+ T cells in immune response against ICC. Secondly, a subset of tumors with "hot" TIME represents potential candidates for ICI, while stimulation of STAT1 pathway could be a potential target to turn "cold" into "hot" TIME in ICC.
The tumor immune microenvironment (TIME) plays a critical role in the immune response In many cancers, including intrahepatic cholangiocarcinoma (ICC). Molecular subtyping of the ICC microenvironment already revealed inter-tumoral heterogeneity with variant profiles of immune cell infiltrates. A recent study created an in-depth immune cell atlas of the TIME in biliary tract cancers and could demonstrate the relevance of specific immune cell subpopulations on patient outcome. We are able to provide a distinctive characterization of TIME, separating tumor epithelial- and stroma areas, in a large and representative ICC cohort using digitalized image analysis on tissue microarrays (TMA) as well as multiplex imaging mass cytometry (IMC). The study was designed for identification of immune cell prognosticators allocating institutional ICC patients into a discovery (2008–15) and a validation (2010–19) cohort. Immune cell subpopulations were correlated with clinicopathological characteristics and patient outcome. Our results highlight: i. The important role of CD4+ T cell infiltration in ICC patients; ii. ICC tumors with high density of immune cells associated with PD-L1 expression identifies a subset of patients with variant tumor biology; iii. Stimulation of STAT1 pathway may be a relevant target to turn “
Autres résumés
Type: plain-language-summary
(eng)
The tumor immune microenvironment (TIME) plays a critical role in the immune response In many cancers, including intrahepatic cholangiocarcinoma (ICC). Molecular subtyping of the ICC microenvironment already revealed inter-tumoral heterogeneity with variant profiles of immune cell infiltrates. A recent study created an in-depth immune cell atlas of the TIME in biliary tract cancers and could demonstrate the relevance of specific immune cell subpopulations on patient outcome. We are able to provide a distinctive characterization of TIME, separating tumor epithelial- and stroma areas, in a large and representative ICC cohort using digitalized image analysis on tissue microarrays (TMA) as well as multiplex imaging mass cytometry (IMC). The study was designed for identification of immune cell prognosticators allocating institutional ICC patients into a discovery (2008–15) and a validation (2010–19) cohort. Immune cell subpopulations were correlated with clinicopathological characteristics and patient outcome. Our results highlight: i. The important role of CD4+ T cell infiltration in ICC patients; ii. ICC tumors with high density of immune cells associated with PD-L1 expression identifies a subset of patients with variant tumor biology; iii. Stimulation of STAT1 pathway may be a relevant target to turn “
Identifiants
pubmed: 39359389
doi: 10.1080/2162402X.2024.2406052
pii: 2406052
pmc: PMC11445892
doi:
Substances chimiques
Biomarkers, Tumor
0
B7-H1 Antigen
0
CD274 protein, human
0
STAT1 Transcription Factor
0
Antigens, CD
0
CD68 antigen, human
0
Antigens, Differentiation, Myelomonocytic
0
STAT1 protein, human
0
CD68 Molecule
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2406052Informations de copyright
© 2024 The Author(s). Published with license by Taylor & Francis Group, LLC.
Déclaration de conflit d'intérêts
No potential conflict of interest was reported by the author(s).