TY  - JOUR
AU  - Steinfass, Tamara
AU  - Poelchen, Juliane
AU  - Sun, Qian
AU  - Mastrogiulio, Giovanni
AU  - Novak, Daniel
AU  - Vierthaler, Marlene
AU  - Pardo, Sandra
AU  - Federico, Aniello
AU  - Hüser, Laura
AU  - Hielscher, Thomas
AU  - Carretero, Rafael
AU  - Offringa, Rienk
AU  - Altevogt, Peter
AU  - Umansky, Viktor
AU  - Utikal, Jochen
TI  - Secretogranin II influences the assembly and function of MHC class I in melanoma.
JO  - Experimental hematology & oncology
VL  - 12
IS  - 1
SN  - 2162-3619
CY  - London
PB  - Biomed Central
M1  - DKFZ-2023-00523
SP  - 29
PY  - 2023
N1  - #EA:A370#LA:A370#
AB  - Melanoma is the deadliest form of skin cancer showing rising incidence over the past years. New insights into the mechanisms of melanoma progression contributed to the development of novel treatment options, such as immunotherapies. However, acquiring resistance to treatment poses a big problem to therapy success. Therefore, understanding the mechanisms underlying resistance could improve therapy efficacy. Correlating expression levels in tissue samples of primary melanoma and metastases revealed that secretogranin 2 (SCG2) is highly expressed in advanced melanoma patients with poor overall survival (OS) rates. By conducting transcriptional analysis between SCG2-overexpressing (OE) and control melanoma cells, we detected a downregulation of components of the antigen presenting machinery (APM), which is important for the assembly of the MHC class I complex. Flow cytometry analysis revealed a downregulation of surface MHC class I expression on melanoma cells that showed resistance towards the cytotoxic activity of melanoma-specific T cells. IFNγ treatment partially reversed these effects. Based on our findings, we suggest that SCG2 might stimulate mechanisms of immune evasion and therefore be associated with resistance to checkpoint blockade and adoptive immunotherapy.
KW  - HLA (Other)
KW  - MHC class I (Other)
KW  - Melanoma (Other)
KW  - Prognosis (Other)
KW  - SCG2 (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:36906639
C2  - pmc:PMC10007832
DO  - DOI:DOI: 10.1186/s40164-023-00387-1
UR  - https://inrepo02.dkfz.de/record/274237
ER  -