Platelet-expressed immune checkpoint regulator GITRL in breast cancer.
Biomarkers, Tumor
Blood Platelets
/ metabolism
Breast Neoplasms
/ genetics
Cell Line, Tumor
Female
Flow Cytometry
Gene Expression Regulation, Neoplastic
Glucocorticoid-Induced TNFR-Related Protein
/ genetics
Humans
Immune Checkpoint Proteins
/ genetics
Immunophenotyping
Lymphocytes
/ immunology
Odds Ratio
Platelet Activation
Platelet Aggregation
Tumor Necrosis Factors
/ genetics
Breast cancer
GITRL
Immune checkpoint
Platelets
Journal
Cancer immunology, immunotherapy : CII
ISSN: 1432-0851
Titre abrégé: Cancer Immunol Immunother
Pays: Germany
ID NLM: 8605732
Informations de publication
Date de publication:
Sep 2021
Sep 2021
Historique:
received:
30
06
2020
accepted:
17
01
2021
pubmed:
5
2
2021
medline:
24
8
2021
entrez:
4
2
2021
Statut:
ppublish
Résumé
Owing to their key role in several diseases including cancer, activating and inhibitory immune checkpoint molecules are increasingly exploited as targets for immunotherapy. Recently, we demonstrated that platelets, which largely influence tumor progression and immune evasion, functionally express the ligand of the checkpoint molecule GITR. This immunoreceptor modulates effector functions of T cells and NK cells with its function varying dependent on cellular context and activation state. Here, we provide a comparative analysis of platelet-derived GITRL (pGITRL) in breast cancer patients and healthy volunteers. The levels of pGITRL were found to be higher on platelets derived from cancer patients and appeared to be specifically regulated during tumor progression as exemplified by several clinical parameters including tumor stage/grade, the occurrence of metastases and tumor proliferation (Ki67) index. In addition, we report that pGITRL is upregulated during platelet maturation and particularly induced upon exposure to tumor-derived soluble factors. Our data indicate that platelets modulate the GITR/GITRL immune checkpoint in the context of malignant disease and provide a rationale to further study the GITR/GITRL axis for exploitation for immunotherapeutic intervention in cancer patients.
Identifiants
pubmed: 33538861
doi: 10.1007/s00262-021-02866-y
pii: 10.1007/s00262-021-02866-y
pmc: PMC8360840
doi:
Substances chimiques
Biomarkers, Tumor
0
Glucocorticoid-Induced TNFR-Related Protein
0
Immune Checkpoint Proteins
0
TNFRSF18 protein, human
0
TNFSF18 protein, human
0
Tumor Necrosis Factors
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2483-2496Subventions
Organisme : Mainz Research School of Translational Biomedicine
ID : TransMed
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : Deutsche Forschungsgemeinschaft
ID : MA 8774/1-1
Organisme : Deutsche Forschungsgemeinschaft
ID : ZUK 63
Organisme : Deutsche Forschungsgemeinschaft
ID : 374031971
Organisme : Deutsche Forschungsgemeinschaft
ID : 39090067
Organisme : Deutsche Forschungsgemeinschaft
ID : SA1360/7-3
Organisme : Deutsche Forschungsgemeinschaft
ID : 70112914
Organisme : Wilhelm Sander-Stiftung
ID : 2007.115.3
Informations de copyright
© 2021. The Author(s).
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