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SOX10 Inhibits T Cell Recognition by Inducing Expression of the Immune Checkpoint Molecule PD-L1 in A375 Melanoma

Kenta Sasaki1,2, Yoshihiko Hirohashi3, Kenji Murata1

  • 1Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan.

Anticancer Research
|March 28, 2023
PubMed
Abstract

Insights

SRY-related HMG-box 10 (SOX10) drives immune suppression in melanoma by increasing programmed death-1 ligand 1 (PD-L1) expression. This SOX10-PD-L1 axis reduces T cell effectiveness against melanoma cells.

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • Malignant melanoma is an immunogenic cancer.
  • SOX10 is a transcription factor crucial for melanoma initiation and a diagnostic marker.
  • SOX10 influences melanoma immune evasion by regulating immune checkpoint molecules.

Purpose of the Study:

  • To investigate the relationship between SOX10 and programmed death-1 ligand 1 (PD-L1) expression in melanoma.
  • To understand SOX10's role in melanoma's immune suppressive mechanisms.

Main Methods:

  • SOX10 overexpression and knockdown were achieved via gene and siRNA transfection in A375 melanoma cells.
  • PD-L1 expression was quantified using flow cytometry and western blotting.
  • T cell response was assessed via IFNγ ELISPOT assay using NY-ESO-1 specific TCR-transduced T cells.

Main Results:

  • SOX10 overexpression led to increased PD-L1 expression.
  • SOX10 knockdown resulted in decreased PD-L1 expression.
  • SOX10 overexpression reduced melanoma cell susceptibility to NY-ESO-1 specific TCR-T cells.

Conclusions:

  • SOX10 contributes to melanoma's intrinsic immune suppression.
  • SOX10 promotes immune evasion in melanoma through PD-L1 expression.
Keywords:
MelanomaPD-L1SOX10immunological resistance

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