Abstract B061: Association of leukocyte inhibitory immunoglobulin-like transcript 3 (ILT3) with ovarian cancer and prevention of its expression by dietary supplementation of Ashwagandha (Withania somnifera)

• Published in: Cancer immunology research 2016-01, Vol.4 (1_Supplement), p.B061-B061
• Main Authors: Gupta, Natasha, Sharma, Sameer, Edassery, Seby L., Bahr, Janice M., Franklin, Lindsey, Paulsen, Erika, Bitterman, Pincas, Barua, Animesh
• Format: Article
• Language: English
• ISSN: 2326-6066; 2326-6074
• DOI: 10.1158/2326-6074.CRICIMTEATIAACR15-B061

Background: Tumor-induced immunosuppression may be a reason for aggressive metastasis of ovarian cancer (OVCA). OVCA is a fatal malignancy of women with the highest case to death ratio among gynecological cancers. Most of the OVCA patients are postmenopausal women affected severely by the toxicity of current chemotherapeutics and danger of radiotherapy. Thus immunotherapy may be an alternative option for OVCA patients. Because OVCA mainly disseminates in the peritoneal cavity, immune functions in the tumor environment plays a crucial role in its progression. However, the mechanism(s) of immunosuppression by ovarian tumors are not well understood. Expression of leukocyte inhibitory immunoglobulin-like transcript 3 (ILT3, a member of inhibitory receptor family) by the tumors is one of the mechanisms in tumor-induced immunosuppression. Prevention or blocking of ILT3 expression may enhance anti-tumor immune responses. Information on ILT3 expression in OVCA and its prevention is not available. Herbs have long been used in traditional medicine against many human diseases including cancers. Ashwagandha or Winter Cherry (ASH, Withania somnifera), a herb known for its anti-tumor property, may enhance anti-tumor immunity by reducing ILT3 expression. Objectives: The goal of this study was to determine whether ovarian malignant tumors express ILT3 and whether dietary supplementation of ASH root powder reduces ILT3 expression in OVCA. Methods: Two experiments were performed. In the first one, archived specimen from normal ovaries of postmenopausal women (n=10), benign tumors (cystadenomas/adenofibromas, n=10) and ovarian malignant tumors (papillary serous) at early (n=7) and late stages (n=10) were examined for ILT3 expression. In the second group, laying hens, a preclinical model of spontaneous OVCA, were used. Healthy hens with normal ovaries or hens with early stage OVCA (selected by transvaginal ultrasound scanning) were divided into 3 groups and provided with basal diet (control) or diet supplemented with either 1% or 2% ASH root powder for 90 days. Each group had 20 hens (15 healthy, 5 with early stage OVCA). Hens were euthanized thereafter and gross morphology including normal and tumor stages were recorded, serum, ovarian tissues with or without cancer were collected and processed for ILT3 expression by immunohistochemistry (IHC), Western blotting or gene expression analysis. Differences in ILT3 expression among different pathological or supplemented groups wer