TGF-? in uveal melanoma

Abstract

Uveal melanoma is the most common primary ocular cancer among adults and patients with distant metastases seldom survive longer than a year. Melanomas of the eye have the advantage of growing in the special environment of an immune privileged site and it has long been shown, that the special immunosuppressive properties of the intraocular microenvironment are strongly mediated by cytokines, especially transforming growth factor‐beta (TGF‐beta). Here, we sought to investigate the presence of TGF‐β in surgically removed uveal melanoma specimens using immunohistochemical methods to verify possible autocrine mechanisms. Immunocytochemistry for pan‐TGF‐β and TGF‐β2 was performed on 13 melanoma specimens using an alkaline phosphatase labeling procedure. Melanocytic origin of the tumors was confirmed by HMB‐45 staining. All tissue samples exhibited positive staining using either pan‐TGF‐β or TGF‐β2 antibody regardless of cell‐type, size of the tumor, or tumor location. The intensity of staining did not vary significantly within a given tumor. All tumors stained positive against the HMB‐45 antibody. Many cytokines have been found to act on melanoma tumors. The presence of the TGF‐β2 isoform in all specimens points to progressive tumor‐growth as has been shown for melanomas of the skin. Based on our immunohistochemical findings and the immunosuppressive properties of TGF‐β, we suppose that ocular melanomas should be able to create their own immunosuppressive environment even in the uvea, which might be a non‐privileged site. Microsc. Res. Tech. 52:396–400, 2001. © 2001 Wiley‐Liss, Inc.

Intratumoral forkhead box P3‐positive regulatory T cells predict poor survival in cyclooxygenase‐2–positive uveal melanoma

“…12-14 TGF-b is of particular interest in uveal tissue, because it is 1 of the factors that contribute to the immune-privileged environment of UM and reportedly has prognostic relevance for the course of disease. 3 In addition, TGF-b and COX-2 have synergistic effects within the process of carcinogenesis. 36 For future studies, it will be of interest to evaluate the association between TGF-b in combination with COX-2/ PGE 2 and Tregs, especially with regard to its prognostic value in UM.…”

Inflammation in uveal melanoma

“…TGF-b may be produced by the tumour cells or by the inflammatory cells. 43 Other tumour cell products, such as IL-10, CSF-1, and chemokines (eg, CCL2), can modulate macrophages to become M2-like, cancer-promoting cells. That macrophages can stimulate tumour growth in the eye is a result, in part, of endogenously produced IL-1.…”

Blood Biomarkers for Uveal Melanoma

“…b 2 -microglobulin, the light chain of the HLA class I complex, has been associated with metastasis in uveal melanoma and is measurable in blood [41]. Immune cytokines and cytokine receptors associated with uveal melanoma progression that can be measured in blood include IL-6 [42], TGF-b [26,43], IL-2 receptor [44] and macrophage migration i nhibitory factor [45].…”