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

Abstract

BackgroundThe 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.MethodsA 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.ResultsThe 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).ConclusionsNF-κB plays a major role in acral MM invasion, by decreasing the number of CD8+ T cells in acral MM.

High Expression of COX-2 Associated with the Depth of Invasion on Acral Melanoma by Increasing TGF-β1

“…Several studies have shown that the increased activity of NF-kB will stimulate the expression of COX-2 inflammatory factors. 8,19 The result of this study is consistent with Usman et al's research which states that there is an association between NF-κβ and CD8 and the depth of invasion of AM. An increase in NF-κβ which is a transcription factor plays a role in stimulating COX-2 expression so that the amount increases.…”

“…Several studies have shown that the increased activity of NF-kB will stimulate the expression of COX-2 inflammatory factors. 8 , 19 …”

“…An increase in NF-κβ which is a transcription factor plays a role in stimulating COX-2 expression so that the amount increases. 8 …”

“…Several studies have also shown that the increased activity of NF-κβ will stimulate the expression of COX-2 inflammatory factors. 8 COX-2 is a pleiotropic enzyme and produced by a variety of malignant tumor cells. COX-2 plays a role in the process of carcinogenesis and resistance of malignant tumor cells to chemotherapy and radiotherapy.…”

“…An increase in NF-κβ which is a transcription factor plays a role in stimulating COX-2 expression so that the amount increases. 8 The study of Goulet et al found shallow levels of COX-2 expression in early-stage melanoma but obtained very high levels of COX-2 expression in melanomas with higher stages and metastasis. 24 Significant results were obtained in the association between COX-2 and tumor stage in MM that the higher the MM stage, the stronger COX-2 expression was obtained.…”