Alternative macrophage polarisation associated with resistance to anti-PD1 blockade is possibly supported by the splicing of FKBP51 immunophilin in melanoma patients.
Aged
Antibodies, Monoclonal, Humanized
/ therapeutic use
B7-H1 Antigen
/ antagonists & inhibitors
Drug Resistance, Neoplasm
/ immunology
Female
Humans
Immune Checkpoint Inhibitors
/ therapeutic use
Immunotherapy
/ methods
Macrophage Activation
/ immunology
Macrophages
/ immunology
Male
Melanoma
/ drug therapy
Middle Aged
Nivolumab
/ therapeutic use
Protein Isoforms
T-Lymphocytes, Regulatory
/ immunology
Tacrolimus Binding Proteins
/ metabolism
Journal
British journal of cancer
ISSN: 1532-1827
Titre abrégé: Br J Cancer
Pays: England
ID NLM: 0370635
Informations de publication
Date de publication:
06 2020
06 2020
Historique:
received:
19
11
2019
accepted:
24
03
2020
revised:
25
02
2020
pubmed:
23
4
2020
medline:
20
3
2021
entrez:
23
4
2020
Statut:
ppublish
Résumé
FKBP51 immunophilin is abundantly expressed by immune cells. Co-inhibitory immune receptor signalling generates the splicing isoform FKBP51s. Tregs stained by FKBP51s are increased in melanoma patients and their counts are associated with anti-CTLA-4 response. An expansion of FKBP51s Co-cultures of organoids and autologous lymphocytes were used to confirm that tumour T-cell interaction can induce FKBP51s. PBMC immunophenotype and flow cytometry served to assess and monitor FKBP51s FKBP51s FKBP51s may guide in the selection and monitoring of melanoma patient candidates to immune-checkpoint-targeted therapy. Manipulation of FKBP51s may overcome resistance.
Sections du résumé
BACKGROUND
FKBP51 immunophilin is abundantly expressed by immune cells. Co-inhibitory immune receptor signalling generates the splicing isoform FKBP51s. Tregs stained by FKBP51s are increased in melanoma patients and their counts are associated with anti-CTLA-4 response. An expansion of FKBP51s
METHODS
Co-cultures of organoids and autologous lymphocytes were used to confirm that tumour T-cell interaction can induce FKBP51s. PBMC immunophenotype and flow cytometry served to assess and monitor FKBP51s
RESULTS
FKBP51s
CONCLUSIONS
FKBP51s may guide in the selection and monitoring of melanoma patient candidates to immune-checkpoint-targeted therapy. Manipulation of FKBP51s may overcome resistance.
Identifiants
pubmed: 32317723
doi: 10.1038/s41416-020-0840-8
pii: 10.1038/s41416-020-0840-8
pmc: PMC7283486
doi:
Substances chimiques
Antibodies, Monoclonal, Humanized
0
B7-H1 Antigen
0
CD274 protein, human
0
Immune Checkpoint Inhibitors
0
Protein Isoforms
0
Nivolumab
31YO63LBSN
pembrolizumab
DPT0O3T46P
Tacrolimus Binding Proteins
EC 5.2.1.-
tacrolimus binding protein 5
EC 5.2.1.8
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1782-1790Références
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