Abstract 5415: Expression of immunosuppressive leukocyte inhibitory immunoglobulin like transcript 3(ILT3) receptors increases with the development and progression of ovarian tumors

Abstract

Abstract Background: Immunosuppressive tumor microenvironment has been suggested as one of the barriers to anti-tumor immune response in patient with ovarian cancer (OVCA). Leukocyte Inhibitory Receptor Immunoglobulin-like Transcript 3 (ILT3) has been proposed as a factor involved in the suppression of immune response in several malignancies. However, the expression and role of ILT3 in the development and progression of ovarian tumors has not yet been studied. Objective: The goal of this study was to examine the expression and association of ILT3 in ovarian tumors in laying hen, a preclinical model of OVCA in humans. Methods: A cohort of mature White Leghorn laying hens with normal or low egg laying rates were evaluated by transvaginal ultrasound scan (15 normal hens and 30 hens with OVCA).All hens were euthanized and serum and ovarian tissues from all hens were collected and processed for immunohistochemistry (IHC), Western blotting (WB) and RT-PCR. Presence of tumors and tumor staging were confirmed by gross morphology and histology. Expression of ILT3 was examined by IHC, WB and RT-PCR. Results: Immune cell like cells in the ovarian stroma as well as epithelium of the normal ovaries and ovarian tumors expressed ILT3. The intensity of ILT3 expression was significantly higher in hens with OVCA than normal hens. Moreover, the intensity of ILT3 expression varied with histological subtypes of ovarian tumors and was significantly higher in serous OVCA than endometrioid OVCA. A band of approximately 55kDa of ILT3 protein was detected in the homogenates of normal ovarian surface epithelium or tumor epithelium as well as whole normal or ovarian tumor extracts. Similar to IHC observations, protein expression was stronger in hens with OVCA than in normal hens. Conclusion: This is the first study to show that immunosuppressive ILT3 is expressed by ovarian tumor epithelium and the intensity of expression increases as the disease progresses. Thus the results are consistent with the hypothesis that ILT3 may be involved in the suppression of anti-tumor immunity in OVCA. The laying hens may be a useful model to understand the OVCA-associated expression of ILT3. This animal model also offers the opportunity to develop and test anti-ILT3 therapy to enhance anti-tumor immunity against OVCA in humans. Support: Department of Defense (OC#93303) and Elmer Sylvia and Sramek Foundation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5415. doi:1538-7445.AM2012-5415