SOX10 requirement for melanoma tumor growth is due, in part, to immune-mediated effects.
Cell Rep
; 37(10): 110085, 2021 12 07.
Article
in En
| MEDLINE
| ID: mdl-34879275
ABSTRACT
Developmental factors may regulate the expression of immune modulatory proteins in cancer, linking embryonic development and cancer cell immune evasion. This is particularly relevant in melanoma because immune checkpoint inhibitors are commonly used in the clinic. SRY-box transcription factor 10 (SOX10) mediates neural crest development and is required for melanoma cell growth. In this study, we investigate immune-related targets of SOX10 and observe positive regulation of herpesvirus entry mediator (HVEM) and carcinoembryonic-antigen cell-adhesion molecule 1 (CEACAM1). Sox10 knockout reduces tumor growth in vivo, and this effect is exacerbated in immune-competent models. Modulation of CEACAM1 expression but not HVEM elicits modest effects on tumor growth. Importantly, Sox10 knockout effects on tumor growth are dependent, in part, on CD8+ T cells. Extending this analysis to samples from patients with cutaneous melanoma, we observe a negative correlation with SOX10 and immune-related pathways. These data demonstrate a role for SOX10 in regulating immune checkpoint protein expression and anti-tumor immunity in melanoma.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Skin Neoplasms
/
Cell Proliferation
/
SOXE Transcription Factors
/
Melanoma
Type of study:
Prognostic_studies
Limits:
Animals
/
Humans
/
Male
Language:
En
Journal:
Cell Rep
Year:
2021
Type:
Article
Affiliation country:
United States