The Major Role of NF-κB in the Depth of Invasion on Acral Melanoma by Decreasing CD8⁺ T Cells

ABSTRACT

BACKGROUND: The tumor microenvironment including immune surveillance affects malignant melanoma (MM) behavior. Nuclear factor κB (NF-κB) stimulates the transcription of various genes in the nucleus and plays a role in the inflammatory process and in tumorigenesis. CD8⁺ T cells have cytotoxic properties important in the elimination of tumors. However, inhibitory receptors on the cell surface will bind to programmed death-ligand 1 (PD-L1), causing CD8⁺ T cells to lose their ability to initiate an immune response. This study analyzed the association of NF-κB and PD-L1 expression levels and CD8⁺ T-cell counts with depth of invasion of acral MM, which may be a predictor of aggressiveness related to an increased risk of metastasis. METHODS: A retrospective cross-sectional study was conducted in the Department of Anatomical Pathology, Faculty of Medicine, Universitas Padjadjaran/Hasan Sadikin Hospital using 96 cases of acral melanoma. Immunohistochemical staining was performed on paraffin blocks using anti–NF-κB, –PD-L1, and -CD8 antibodies and invasion depth was measured using dotSlide-imaging software. RESULTS: The study showed significant associations between the individual expression of NF-κB and PD-L1 and CD8⁺ T-cell number, with MM invasion depth. NF-κB was found to be a confounding variable of CD8⁺ T-cell number (p < .05), but not for PD-L1 expression (p = .154). Through multivariate analysis it was found that NF-κB had the greatest association with the depth of invasion (p < .001), whereas PD-L1 was unrelated to the depth of invasion because it depends on the number of CD8⁺ T cells (p = .870). CONCLUSIONS: NF-κB plays a major role in acral MM invasion, by decreasing the number of CD8⁺ T cells in acral MM.