Expression of Fas ligand in retinoblastoma

Abstract

BACKGROUND The importance of the Fas‐Fas ligand (FasL) mechanism for the immune evasion by tumors provided a strong rationale for the examination of FasL expression in retinoblastoma. In an earlier publication, the authors reported that invasive retinoblastomas decreased Fas expression. Because to the authors' knowledge there is not much information regarding the effect of FasL expression on retinoblastoma, the authors studied the expression of FasL in retinoblastoma and correlated it with invasiveness. METHODS Thirty‐six archival retinoblastoma specimens were divided into 2 groups. Group A (n = 17) was comprised of specimens from tumors with no invasion and Group B (n = 19) was comprised of specimens from tumors with invasion of the choroid (focal, diffuse), optic nerve (laminar, postlaminar, surgical end), and orbit. Sections were immunostained with a monoclonal antibody to FasL and the immunoreactivity was assessed. RESULTS In Group A, FasL was negative in 100% (17 of 17) of the tumor specimens. In Group B, FasL was expressed in 79% (15 of 19) of the tumor specimens (positive in 9 tumors and heterogeneous in 6 tumors). The difference in FasL expression between the two groups was significant (P < 0.001) CONCLUSIONS Increased expression of FasL was observed in specimens taken from patients with aggressive tumors. Thus, Loss of Fas and gain of aberrant FasL expression were common features of malignant transformation. The data suggested that the Fas/FasL pathway is potentially immunosuppressive and may be involved in the escape of retinoblastoma cells from immune destruction. Cancer 2004. © 2004 American Cancer Society.

The role of nitric oxide synthases and nitrotyrosine in retinoblastoma

“…Additional studies at our institute have shown that there are multiple mechanisms in retinoblastoma that contribute to their invasiveness: Invasive retinoblastoma had 1) decreased metastasis‐suppressor protein nm23‐H1 and nm‐H255; 2) decreased tetraspanin protein KAI1/CD82,56 which contributes to increased motility of tumor cells and to invasion; 3) decreased/absent Fas expression,57 which allows tumor cells to escape from Fas ligand (FasL)‐mediated tumor cell death; 4) elevated FasL expression in invading tumors that may enable them to lyse Fas‐expressing tumor‐infiltrating lymphocytes58; and 5) decreased human leukocyte antigens Class I and II and the antigen‐processing molecules of the Class I pathway,59 which allows the escape of tumor cells from cytotoxic T lymphocyte‐mediated cell death while maintaining resistance to natural killer cell lysis. Hence, these deregulations allow tumors to gain time for the accumulation of critical mutations and/or derangements in the expression of malignancy causing genes, which will provide these tumors with uncontrollable invasive potential.…”

T Cell Apoptosis Was Inhibited by Fas of Antisense Oligonucleotide

“…Collect different experimental groups cells and label Fas antibody according to the method in [2,3] when Fas was labeled. Then Fas expression was detected by FCM.…”

Effects of specific antisense oligonucleotide inhibition of Fas expression on T cell apoptosis induced by Fas ligand

“…CTLinduced apoptosis of cancer cells via Fas pathway is one of the two main ways of CTL killing cancer cells in human body, the other is perforin-based [1]. Some reports found that cancer cells could decrease Fas expression which could escape the immune surveillance and killing, on the other hand, functional FasL expression by certain cancer cell types could induce apoptosis of CTL, especially tumor specific antigen induce Fas-bearing tumor infiltrating lymphocytes (TILs), because they exhibited significantly increased expression of Fas relative to peripheral blood lymphocytes [2][3][4]. In these cases, Fas and FasL may contribute to tumor immune privilege by inducing FasLmediated apoptosis of host CTL and natural killer (NK) cells.…”