TY  - JOUR
A1  - Herrmann, Thomas
A1  - Karunakaran, Mohindar M.
T1  - Butyrophilins: γδ T cell receptor ligands, immunomodulators and more
JF  - Frontiers in Immunology
N2  - Butyrophilins (BTN) are relatives of the B7 family (e.g., CD80, PD-L1). They fulfill a wide range of functions including immunomodulation and bind to various receptors such as the γδ T cell receptor (γδTCR) and small molecules. One intensively studied molecule is BTN3A1, which binds via its cytoplasmic B30.2 domain, metabolites of isoprenoid synthesis, designated as phosphoantigen (PAg), The enrichment of PAgs in tumors or infected cells is sensed by Vγ9Vδ2 T cells, leading to the proliferation and execution of effector functions to remove these cells. This article discusses the contribution of BTNs, the related BTNL molecules and SKINT1 to the development, activation, and homeostasis of γδ T cells and their immunomodulatory potential, which makes them interesting targets for therapeutic intervention.
KW  - butyrophilin
KW  - immune therapy
KW  - T cell receptor
KW  - γδ T cell
KW  - BTN3A1
KW  - BTN2A1
KW  - phosphoantigen
KW  - tumor
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-265944
SN  - 1664-3224
VL  - 13
ER  - 
TY  - JOUR
A1  - Boschert, Verena
A1  - Teusch, Jonas
A1  - Aljasem, Anwar
A1  - Schmucker, Philipp
A1  - Klenk, Nicola
A1  - Straub, Anton
A1  - Bittrich, Max
A1  - Seher, Axel
A1  - Linz, Christian
A1  - Müller-Richter, Urs D. A.
A1  - Hartmann, Stefan
T1  - HGF-induced PD-L1 expression in head and neck cancer: preclinical and clinical findings
JF  - International Journal of Molecular Sciences
N2  - Head and neck squamous cell carcinoma (HNSCC) is a widespread disease with a low survival rate and a high risk of recurrence. Nowadays, immune checkpoint inhibitor (ICI) treatment is approved for HNSCC as a first-line treatment in recurrent and metastatic disease. ICI treatment yields a clear survival benefit, but overall response rates are still unsatisfactory. As shown in different cancer models, hepatocyte growth factor/mesenchymal–epithelial transition (HGF/Met) signaling contributes to an immunosuppressive microenvironment. Therefore, we investigated the relationship between HGF and programmed cell death protein 1 (PD-L1) expression in HNSCC cell lines. The preclinical data show a robust PD-L1 induction upon HGF stimulation. Further analysis revealed that the HGF-mediated upregulation of PD-L1 is MAP kinase-dependent. We then hypothesized that serum levels of HGF and soluble programmed cell death protein 1 (sPD-L1) could be potential markers of ICI treatment failure. Thus, we determined serum levels of these proteins in 20 HNSCC patients before ICI treatment and correlated them with treatment outcomes. Importantly, the clinical data showed a positive correlation of both serum proteins (HGF and sPD-L1) in HNSCC patient’s sera. Moreover, the serum concentration of sPD-L1 was significantly higher in ICI non-responsive patients. Our findings indicate a potential role for sPD-L1 as a prognostic marker for ICI treatment in HNSCC.
KW  - HNSCC
KW  - head and neck cancer
KW  - HGF
KW  - Met
KW  - PD-L1
KW  - immune therapy
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-236220
SN  - 1422-0067
VL  - 21
IS  - 20
ER  -