Aparna Yellapa

Association of interleukin 16 with the development of ovarian tumor and tumor-associated neoangiogenesis in laying hen model of spontaneous ovarian cancer.

Objective Tumor-associated neoangiogenesis (TAN) is an early event in ovarian tumor development. Interleukin 16 (IL-16) is a proangiogenic cytokine that stimulates production of neoangiogenic factors. The goal of this study was to determine the association of IL-16 with tumor development and ovarian TAN in laying hens, an animal model of spontaneous ovarian cancer (OVCA). Methods Sera and ovarian tissues from 3-year-old laying hens were collected and processed for histopathologic, immunoassay, immunohistochemistry, immunoblotting, and molecular biological studies to determine the tissue expression and serum levels of IL-16. Samples were divided into 3 groups based on the diagnosis of the histopathologic ovarian tissue examination, namely, normal (healthy control, n = 81), early (n = 23 including 11 with microscopic OVCA), and late stages (n = 16) of OVCA. Results Serum levels of IL-16 were significantly higher in hens with microscopic, early, and late stages of OVCA than normal hens (P < 0.0001). The frequencies of IL-16+cells in tumor-bearing ovaries were significantly higher than normal hens (P < 0.05). The expression of IL-16 protein and mRNA were stronger in tumor-bearing ovaries than normal ovaries. In addition to ovarian stroma, IL-16 was also expressed by the epithelial cells of the tumor in OVCA hens. Differences in serum levels and ovarian IL-16 expression were not significant among different histological subtypes of OVCA including serous, endometrioid, and mucinous. Similar to the serum levels and ovarian expression of IL-16, the densities of neoangiogenic microvessels were significantly higher in hens with tumor-bearing ovaries than normal hens. Conclusions The results of the study suggest that changes in serum levels of IL-16 are associated with tumor development and TAN. Thus, serum IL-16 levels may be an indicator of ovarian TAN at the early stage of OVCA.

Interleukin 16 expression changes in association with ovarian malignant transformation

OBJECTIVE Long-term unresolved inflammation has been suggested as a risk factor for the development of various malignancies. The goal of this study was to examine whether the expression of interleukin (IL)-16, a proinflammatory cytokine, changes in association with ovarian cancer (OVCA) development. STUDY DESIGN In an exploratory study, changes in IL-16 expression in association with OVCA development and progression were determined using ovarian tissues and serum samples from healthy subjects (n = 10) and patients with benign (n = 10) and malignant ovarian tumors at early (n = 8) and late (n = 20) stages. In the prospective study, laying hens, a preclinical model of spontaneous OVCA, were monitored (n = 200) for 45 weeks with serum samples collected at 15-week interval. Changes in serum levels of IL-16 relative to OVCA development were examined. RESULTS The frequency of IL-16-expressing cells increased significantly in patients with OVCA (P < .001) compared to healthy subjects and patients with benign ovarian tumors. The concentration of serum IL-16 was higher in patients with benign tumors (P < .05) than in healthy subjects and increased further in patients with early-stage (P < .05) and late-stage (P < .03) OVCA. Increase in tissue expression and serum levels of IL-16 in patients with early and late stages of OVCA were positively correlated with the increase in ovarian tumor-associated microvessels. Prospective monitoring showed that serum levels of IL-16 increase significantly (P < .002) even before ovarian tumors become grossly detectable in hens. CONCLUSION This study showed that tissue expression and serum levels of IL-16 increase in association with malignant ovarian tumor development and progression.

Enhancement of ovarian tumor detection with αvβ3 integrin-targeted ultrasound molecular imaging agent in laying hens: a preclinical model of spontaneous ovarian cancer.

Objective Because of the lack of an effective early detection test, ovarian cancer (OVCA) in most cases is detected at late stages and remains a fatal gynecological malignancy. Molecular imaging provides information on the changes associated with the development of a disease at molecular levels. Because angiogenesis is an early event in tumor development, increased expression of &agr;vβ3 integrins by ovarian tumor–associated angiogenic microvessels provides a target for noninvasive ultrasound imaging to detect early-stage OVCA. The goal of this study was to examine the feasibility of &agr;vβ3 integrin–targeted molecular imaging agent in enhancing the detection of spontaneous ovarian tumor in laying hens, a preclinical model of OVCA. Methods The study was conducted in 2 phases, including a cross-sectional exploratory followed by a prospective monitoring of hens for 45 weeks with targeted ultrasound imaging. Changes in ultrasound signal intensity were determined before and after the injection of &agr;vβ3 integrin–targeted imaging agent in hens with spontaneous OVCA. All images were digitally stored. After scanning, ovarian tissues from all hens were collected and processed for histopathologic and immunohistochemical studies. Results Ultrasound signal intensity was significantly (P < 0.001) higher in hens with early-stage OVCA than in normal hens and increased further in late-stage OVCA. Compared with that in normal cases, ultrasound signal intensities increased approximately 19-fold in early stage and 26-fold in late-stage OVCA. Differences in signal enhancement were not observed among different histologic subtypes of OVCA. Higher signal intensities from targeted imaging of ovarian tumors were associated with increased number of &agr;vβ3 integrin–expressing ovarian microvessels. Prospective monitoring of hens with &agr;vβ3 integrin–targeted imaging agent detected OVCA at early stage. Conclusions These results suggest that &agr;vβ3 integrin–targeted imaging agent enhanced the visualization of ovarian tumor–associated angiogenic microvessels in hens with early-stage OVCA and may form a foundation for clinical studies.ObjectiveBecause of the lack of an effective early detection test, ovarian cancer (OVCA) in most cases is detected at late stages and remains a fatal gynecological malignancy. Molecular imaging provides information on the changes associated with the development of a disease at molecular levels. Because angiogenesis is an early event in tumor development, increased expression of &agr;v&bgr;3 integrins by ovarian tumor–associated angiogenic microvessels provides a target for noninvasive ultrasound imaging to detect early-stage OVCA. The goal of this study was to examine the feasibility of &agr;v&bgr;3 integrin–targeted molecular imaging agent in enhancing the detection of spontaneous ovarian tumor in laying hens, a preclinical model of OVCA. MethodsThe study was conducted in 2 phases, including a cross-sectional exploratory followed by a prospective monitoring of hens for 45 weeks with targeted ultrasound imaging. Changes in ultrasound signal intensity were determined before and after the injection of &agr;v&bgr;3 integrin–targeted imaging agent in hens with spontaneous OVCA. All images were digitally stored. After scanning, ovarian tissues from all hens were collected and processed for histopathologic and immunohistochemical studies. ResultsUltrasound signal intensity was significantly (P < 0.001) higher in hens with early-stage OVCA than in normal hens and increased further in late-stage OVCA. Compared with that in normal cases, ultrasound signal intensities increased approximately 19-fold in early stage and 26-fold in late-stage OVCA. Differences in signal enhancement were not observed among different histologic subtypes of OVCA. Higher signal intensities from targeted imaging of ovarian tumors were associated with increased number of &agr;v&bgr;3 integrin–expressing ovarian microvessels. Prospective monitoring of hens with &agr;v&bgr;3 integrin–targeted imaging agent detected OVCA at early stage. ConclusionsThese results suggest that &agr;v&bgr;3 integrin–targeted imaging agent enhanced the visualization of ovarian tumor–associated angiogenic microvessels in hens with early-stage OVCA and may form a foundation for clinical studies.

VEGFR2-Targeted Ultrasound Imaging Agent Enhances the Detection of Ovarian Tumors at Early Stage in Laying Hens, a Preclinical Model of Spontaneous Ovarian Cancer.

Tumor-associated neoangiogenesis (TAN) is an early event in ovarian cancer (OVCA) development. Increased expression of vascular endothelial growth factor receptor 2 (VEGFR2) by TAN vessels presents a potential target for early detection by ultrasound imaging. The goal of this study was to examine the suitability of VEGFR2-targeted ultrasound contrast agents in detecting spontaneous OVCA in laying hens. Effects of VEGFR2-targeted contrast agents in enhancing the intensity of ultrasound imaging from spontaneous ovarian tumors in hens were examined in a cross-sectional study. Enhancement in the intensity of ultrasound imaging was determined before and after injection of VEGFR2-targeted contrast agents. All ultrasound images were digitally stored and analyzed off-line. Following scanning, ovarian tissues were collected and processed for histology and detection of VEGFR2-expressing microvessels. Enhancement in visualization of ovarian morphology was detected by gray-scale imaging following injection of VEGFR2-targeted contrast agents. Compared with pre-contrast, contrast imaging enhanced the intensities of ultrasound imaging significantly (p < 0.0001) irrespective of the pathological status of ovaries. In contrast to normal hens, the intensity of ultrasound imaging was significantly (p < 0.0001) higher in hens with early stage OVCA and increased further in hens with late stage OVCA. Higher intensities of ultrasound imaging in hens with OVCA were positively correlated with increased (p < 0.0001) frequencies of VEGFR2-expressing microvessels. The results of this study suggest that VEGFR2-targeted contrast agents enhance the visualization of spontaneous ovarian tumors in hens at early and late stages of OVCA. The laying hen may be a suitable model to test new imaging agents and develop targeted therapeutics.

Interleukin 16- (IL-16-) Targeted Ultrasound Imaging Agent Improves Detection of Ovarian Tumors in Laying Hens, a Preclinical Model of Spontaneous Ovarian Cancer.

Limited resolution of transvaginal ultrasound (TVUS) scanning is a significant barrier to early detection of ovarian cancer (OVCA). Contrast agents have been suggested to improve the resolution of TVUS scanning. Emerging evidence suggests that expression of interleukin 16 (IL-16) by the tumor epithelium and microvessels increases in association with OVCA development and offers a potential target for early OVCA detection. The goal of this study was to examine the feasibility of IL-16-targeted contrast agents in enhancing the intensity of ultrasound imaging from ovarian tumors in hens, a model of spontaneous OVCA. Contrast agents were developed by conjugating biotinylated anti-IL-16 antibodies with streptavidin coated microbubbles. Enhancement of ultrasound signal intensity was determined before and after injection of contrast agents. Following scanning, ovarian tissues were processed for the detection of IL-16 expressing cells and microvessels. Compared with precontrast, contrast imaging enhanced ultrasound signal intensity significantly in OVCA hens at early (P < 0.05) and late stages (P < 0.001). Higher intensities of ultrasound signals in OVCA hens were associated with increased frequencies of IL-16 expressing cells and microvessels. These results suggest that IL-16-targeted contrast agents improve the visualization of ovarian tumors. The laying hen may be a suitable model to test new imaging agents and develop targeted anti-OVCA therapeutics.

Abstract A64: Association of interleukin 16 with early metastasis of ovarian tumors

Introduction: Ovarian cancer (OVCA) differs from other malignancies in its specific dissemination pattern that the tumor typically spreads in a diffuse intra-abdominal fashion rather than systemic circulation. Interactions among different cell types and their secretory products in the tumor microenvironment may contribute to the tumor development and metastasis. Interleukin 16 (IL-16) is a chemoattractant and pro-angiogenic cytokine involved in multiple immunopathobiological processes. IL-16 is expressed by several cell types including CD8 T cells and macrophages and occasionally by malignant cells. IL-16 expression is reported to be increased in several tumors including OVCA. Thus, IL-16 may be involved in the development and metastasis of ovarian tumors, if so, how IL-16 enhances tumor metastasis is not known. CD9, a member of tetraspanin family, has been implicated in the regulation of cell proliferation, invasion and motility. Emerging studies reported CD9 as a receptor for IL-16. Objectives: The goal of this study was to determine (1) whether IL-16 is associated with ovarian tumor metastasis in the vicinity of tumors including the omentum and (2) if so, to determine how IL-16 is associated with ovarian tumor metastasis. In this study we examined association of IL-16 and its receptor (CD9) expression with respect to ovarian tumor development and progression. The association of CD8+T cells and IL-16 expression during tumor initiation was examined in laying hens, an animal model of spontaneous OVCA. Methods: Experiment-1: Tumor specimen from patients with serous OVCA (10 early and 20 late stages), serous benign ovarian tumors (n=10) and normal (n=5, from patients underwent hysterectomies for non-ovarian disease) and omental tissues (n= 5, each of OVCA and benign) were used. Changes in IL-6 and CD9 expression in tumor tissues (ovaries and omentum) were examined by immunohistochemistry, proteomics and by quantitative polymerase chain reaction (qPCR). Experiment-II: Laying hens with normal ovaries (n=10) or microscopic OVCA (n=10) were examined for CD8 T cells and IL-16 expressing cells as mentioned above. The correlation between the IL-16 and CD8+ T cells were examined. In addition, to examine the effects of IL-16 on CD9 expression, normal ovarian surface epithelial (OSE) cells were treated with recombinant IL-16 protein. Results: Compared with normal ovaries and benign tumors, the frequencies of IL-16 expressing cells were significantly high in early stage OVCA ( P P Conclusions: The results of the present study suggest that increased IL-16 expression may be associated with enhanced CD9 expression which may be a factor for ovarian tumor progression and metastasis to the omental tissues. Increased CD8+ T cells in the tumor vicinity suggests that CD8+ T cells may be a source of enhanced IL-16 expression in developing ovarian tumors. Support: DOD award # W81XWH-11-1-0510 Citation Format: Aparna Yellapa, Pincas Bitterman, Jacques S. Abramowicz, Janice M. Bahr, Sameer Sharma, Sanjib Basu, Animesh Barua. Association of interleukin 16 with early metastasis of ovarian tumors. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: From Concept to Clinic; Sep 18-21, 2013; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2013;19(19 Suppl):Abstract nr A64.

Abstract 1689: Ovarian tumor-induced CISH expression is an immune checkpoint for NK cells

Background: Non-specificity of symptoms in early stages of ovarian cancer (OVCA), lack of an early detection test and inefficient chemotherapy regimens lead to frequent recurrence and high mortality rates. OVCA differs from other malignancies as it disseminates by diffusion in the peritoneal cavity. Local immune function is critical and NK cells provide a first line of defense against a developing tumor. Tumors escape NK cell recognition by cleaving off ligands (MICA/B) for NK cell receptors (NKG2D) from their surface. However, preventing the cleaving of ligands does not improve tumor recognition by NK cells to desired levels, suggesting the existence of an additional inhibitory mechanism. Cytokines, including IL-15, play important roles in the proliferation and activation of NK cells. Nevertheless, longstanding exposure to cytokines induces exhaustion of NK cells through expression of CISH (Cytokine-inducible SH2-containing protein). The goal of this study was to examine whether NK cells in ovarian tumors express CISH and whether CISH expression is associated with tumor progression. Materials and methods: This study was conducted in an exploratory design using normal ovaries from postmenopausal women (60-80 years old, n=10), malignant ovarian tumors at early and late stages (n=12 from each stage, 3 from each of 4 histological OVCA types). Localization of CISH-expressing NK cells and expression of GRP78, a marker of cellular stress, were examined by immunohistochemistry (IHC) using paraffin sections. Representative samples were used for immunoblotting (WB) and gene expression studies. Results: Intense staining for CISH was observed for NK cells with occasional staining of malignant cells. Compared with normal ovaries, the population of CISH-expressing NK cells was greater in OVCA at early stage and increased further at late stages. The population of CISH-expressing NK cells was higher in serous OVCA at early stage as compared to other histological types at early stages. However, significant differences were not observed in the population of CISH-expressing NK cells among different histological types of OVCA at late stages. Immunoblotting showed stronger bands at ~30kDa for CISH for malignant tumors at early and late stages. Expression of GRP78 was significantly greater in ovarian tumors as compared with normal ovaries and increased further in OVCA at late stages. These results suggest the presence of cellular stress in ovarian malignant tumors and in their microenvironment are conducive to express a marker of exhaustion (CISH) by NK cells, which may suppress their anti-tumor functions. Thus, CISH may be an immune checkpoint for NK cells. Conclusion: The results of this study suggest that ovarian tumor development and progression is associated with increased expression of CISH by malignant cells and NK cells. Tumor-induced CISH expression may be associated with decreased anti-tumor function of NK cells. Support: NIH CA187309 Citation Format: Amy K. Stasik, Aparna Yellapa, Pincas Bitterman, Sameer Sharma, Sanjib Basu, Animesh Barua. Ovarian tumor-induced CISH expression is an immune checkpoint for NK cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1689.

Abstract AS14: Contrast enhanced interleukin 16 targeted imaging detects ovarian tumor at early stage

Background: The high rate of death of ovarian cancer (OVCA) patients can be reduced if it is detected at early stage. Neither suggested serum markers nor the currently available traditional transvaginal ultrasound (TVUS) imaging or their combinations can detect OVCA at early stage. No imaging target in the ovary for TVUS imaging corresponding to the suggested serum markers has been defined. Moreover, due to the limited resolution, TVUS imaging cannot detect OVCA at early stage. Thus, new imaging target(s) together with improvement in resolution is necessary for early OVCA detection by TVUS imaging. Interleukin 16 (IL-16), a proinflammatory cytokine, associated with longstanding unresolved inflammation due to frequent ovulation, has been reported to be increased during OVCA development. IL-16 is expressed by the ovarian malignant cells and tumor associated neoangiogenic (TAN) microvessels. Thus IL-16 represents a potential marker of early OVCA which can be detected in vivo by TVUS imaging provided a molecular targeted contrast enhanced imaging agent can be developed. Objective: The goal of this study was to develop and test the efficacy of molecular (IL-16)-targeted ultrasound imaging probe for the detection of early OVCA. Materials and Methods: 3-years old (n=150) White Leghorn laying hens with normal or low egg laying rates or stopped-egg laying were scanned by TVUS before and after intravenous injection with IL-16-targeted microbubbles. IL-16-targeted imaging agents were prepared by conjugating anti-chicken IL-16 antibodies with Targetster® containing microbubbles (Targeson Inc, San Diego). All images were archived and analyzed offline. Serum samples were collected, hens were euthanized, ovarian tissues were processed for paraffin or frozen sections and nuclear matrix protein (NMP) extraction. Ovarian tumors were confirmed by gross morphology and routine histology. Sera were tested for anti-NMP antibodies (a marker of malignant nuclear transformation) and IL-16 levels by immunoassay and 1- & 2D-Western blot (WB). The frequencies of IL-16 expressing cells were determined by immunohistochemistry (IHC). Results: IL-16-targeted microbubbles bounded with ovarian tumors and appeared as shining mass of irregular-shape. Compared with non-targeted, IL-16-targeted imaging increased the visualization of ovarian tumors remarkably. All hens with suspected tumor mass (n=23, 7 early and 16 late stages) were detected by IL-16-targeted imaging and confirmed by gross examination. The frequency of IL-16 expressing cells detected by IHC confirmed the prediction of targeted ultrasound imaging. Serum levels of IL-16 were higher in OVCA hens than in normal hens and correlated with the frequencies of IL-16 expressing cells and ovarian TAN vessels. Prevalence of anti-NMP antibodies were not detected in normal hens while all hens with OVCA were positive. Immunoreactive tumor antigens (NMPs) of 50-80kDa were detected by 2D-WB. Conclusion: IL-16-targeted ultrasound imaging enhanced the visualization of ovarian tumors remarkably. The enhanced intensity of IL-16-targeted imaging was correlated with serum IL-16 levels and the prevalence of anti-NMP antibodies. Thus, IL-16-targeted imaging in association with serum anti-NMP antibodies may improve OVCA detection at early stage. These results will form a foundation for a clinical study. Support: Dept. of Defense award # W81XWH-12-1-0460. Citation Format: Animesh Barua, Aparna Yellapa, Pincas Bitterman, Janice M Bahr, Sanjib Basu, Sameer Sharma, Jacques S. Abramowicz. Contrast enhanced interleukin 16 targeted imaging detects ovarian tumor at early stage [abstract]. In: Proceedings of the 10th Biennial Ovarian Cancer Research Symposium; Sep 8-9, 2014; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(16 Suppl):Abstract nr AS14.

Abstract 4641: IL-16 in association with VEGFR-2 detect early tumor associated changes in the ovary.

Background: Ovarian cancer (OVCA) is a lethal malignancy of women with high rate of death among gynecological cancers. Due to the lack of an effective early detection test, OVCA in most cases are detected at late stage. Interleukin (IL)-16 is a cytokine involved in multiple immunopathobiological processes including inflammatory responses and production of proangiogenic cytokines. IL-16 is expressed by malignant epithelium and secreted in serum. Ovarian malignant transformation is followed by neovascularization and vascular endothelial growth factor receptor-2 (VEGFR-2) is a marker of tumor associated neovascularization (TAN). Thus, IL-16 and VEGFR-2 represent markers of OVCA at early stage may constitute an early detection test for OVCA. Objectives: The goal of this study was to determine whether IL-16 expression is associated with ovarian malignant transformation and to examine association between serum IL-16 levels and VEGFR-2 expression by TAN vessels during ovarian tumor development. Materials and methods: Normal (n =15) White Leghorn laying hens (3-4 years old) or hens with ovarian tumors (n=32) were selected by contrast enhanced transvaginal ultrasound scanning. Following serum collection, hens were euthanized, tissues were processed for routine histology, immunohistochemistry (IHC), protein and gene expression studies. Ovarian tumors were confirmed by gross morphology and microscopy. Expression of IL-16 by ovarian malignant epithelium and VEGFR-2 by ovarian TAN vessels were determined by IHC, immunoblotting and quantitative PCR. Serum IL-16 levels were determined by immunoassay. Correlation between serum IL-16 levels and frequencies of VEGFR-2 expressing microvessels were examined. Results: The intensity of IL-16 expression by normal ovarian epithelium was very weak (n=15). In contrast, the staining intensity of IL-16 by malignant epithelium increased significantly (p Conclusion: IL-16 expression by ovarian malignant epithelium and its serum levels are associated with ovarian malignant transformation and correlated with VEGFR-2 expression. Thus IL-16 may be a useful serum marker and in combination with VEGFR-2 may detect OVCA at early stage. These findings will facilitate clinical studies to establish a non-invasive early OVCA detection test. Support: DOD Award # W81XWH-12-1-0460. Citation Format: Aparna Yellapa, Pincas Bitterman, Jacques S. Abramowicz, Janice M. Bahr, Sanjib Basu, Sameer Sharma, Animesh Barua. IL-16 in association with VEGFR-2 detect early tumor associated changes in the ovary. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4641. doi:10.1158/1538-7445.AM2013-4641

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

Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL 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