Journal Article (Letter)

DKFZ-2023-00523

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Secretogranin II influences the assembly and function of MHC class I in melanoma.

Steinfass, T. (First author)DKFZ* ; Poelchen, J.DKFZ* ; Sun, Q.DKFZ* ; Mastrogiulio, G.DKFZ* ; Novak, D.DKFZ* ; Vierthaler, M. ; Pardo, S.DKFZ* ; Federico, A.DKFZ* ; Hüser, L.DKFZ* ; Hielscher, T.DKFZ* ; Carretero, R.DKFZ* ; Offringa, R.DKFZ* ; Altevogt, P.DKFZ* ; Umansky, V.DKFZ* ; Utikal, J. (Last author)DKFZ*

2023
Biomed Central London

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Please use a persistent id in citations: doi:DOI: 10.1186/s40164-023-00387-1  doi:DOI: 10.1186/s40164-023-00387-1

Abstract: 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.

Keyword(s): HLA ; MHC class I ; Melanoma ; Prognosis ; SCG2

Note: #EA:A370#LA:A370#

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Contributing Institute(s):

1. KKE Dermatoonkologie (A370)
2. DKFZ -Bayer Healthcare Joint (D220)
3. B062 Pädiatrische Neuroonkologie (B062)
4. C060 Biostatistik (C060)
5. Molekulare Grundlagen Gastrointestinaler Tumoren (D200)

Research Program(s):

1. 311 - Zellbiologie und Tumorbiologie (POF4-311) (POF4-311)

Appears in the scientific report 2023

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Database coverage:
; ; Article Processing Charges ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DOAJ Seal ; Ebsco Academic Search ; Essential Science Indicators ; Fees ; IF >= 10 ; JCR ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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