RT Journal Article
SR Electronic
T1 SOX10 Inhibits T Cell Recognition by Inducing Expression of the Immune Checkpoint Molecule PD-L1 in A375 Melanoma Cells
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 1477
OP 1484
DO 10.21873/anticanres.16296
VO 43
IS 4
A1 KENTA SASAKI
A1 YOSHIHIKO HIROHASHI
A1 KENJI MURATA
A1 TOMOYUKI MINOWA
A1 MUNEHIDE NAKATSUGAWA
A1 AIKO MURAI
A1 YUKA MIZUE
A1 TERUFUMI KUBO
A1 TAKAYUKI KANASEKI
A1 TOMOHIDE TSUKAHARA
A1 SADAHIRO IWABUCHI
A1 SHINICHI HASHIMOTO
A1 HISASHI UHARA
A1 AKEMI ISHIDA-YAMAMOTO
A1 TOSHIHIKO TORIGOE
YR 2023
UL http://ar.iiarjournals.org/content/43/4/1477.abstract
AB Background/Aim: Malignant melanoma is a fatal skin cancer and is among the most immunogenic malignancies expressing melanoma-differentiation antigens and neoantigens. SRY-related HMG-box 10 (SOX10) is a transcription factor and a neural-crest differentiation marker that is used as a diagnostic marker for melanoma whilst playing a role in melanoma initiation through activation of the SOX10-MITF axis. SOX10 was shown to play a role in melanoma initiation by inducing expression of immune checkpoint molecules (e.g., HVEM and CEACAM1). In this study, we aimed to investigate the relationship between SOX10 and the expression an immune checkpoint molecule, programmed death-1 ligand 1 (PD-L1). Materials and Methods: SOX10 overexpression and knockdown was performed using SOX10 gene transfection and SOX10 siRNA transfection into A375 melanoma cells. PD-L1 expression was assessed by flow cytometry and western blotting. T cell response was evaluated using NY-ESO-1 specific TCR-transduced T (TCR-T) cells by IFNγ ELISPOT assay. Results: SOX10 overexpression increased the expression of PD-L1, whereas SOX10 knockdown, using siRNA, decreased its expression. IFNγ ELISPOT assay revealed that overexpression of SOX10 decreased the susceptibility of cells to NY-ESO-1-specific TCR-T cells. Conclusion: SOX10 has a role in the intrinsic immune suppressive mechanisms of melanoma through expression of PD-L1.