Abstract 1679: Immunotherapeutic strategies targeting CXCR4 axis plus γ/δ T cells in treating ovarian cancer

• Published in: Cancer research (Chicago, Ill.) Ill.), 2015-08, Vol.75 (15_Supplement), p.1679-1679
• Main Authors: Liu, Chao Lien, Mao, Tsui Lien
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2015-1679

Ovarian carcinoma is the most crucial and difficult problem for therapeutic treatment in gynecological malignancies, which requires great efforts for an effective solution. Molecular studies have shown that chemokine stromal cell-derived factor-1 (SDF-1)/CXCL12 and its receptor CXCR4 are the key determinants of tumor initiation, progression and metastasis in ovarian carcinoma. It is also believed that blocking CXCR4-CXCL12 pathway plays potential roles in treating ovarian cancer patients. Recent studies also showed that the cytotoxic function of gamma delta (γ/δ) T lymphocytes could efficiently kill ovarian CSCs (cancer stem cells) and present a promising immunotherapy for ovarian cancer. To investigate how the CXCL12/CXCR4 pathway is involved in the regulation of ovarian cancer. We eliminated the expression of CXCR4 in different ovarian cancer cell lines using CXCR4 antagonist (e.g., AMD3100) and CXCR4 shRNA silencing to prevent the CXCR4/CXCL12 axis interaction. Besides, up to 78% of γ/δ T cells was expanded in-vitro using aminobisphosphonates plus low-dose interleukin-2 for the therapeutic investigating. The therapeutic effects following different treatments were measured. First, our results showed that blocking of Cxcr4/Cxcl12 axis by AMD3100 reduced around 37% on cell survival rate. Similar results were also observed in the CXCR4-shRNA silencing ovarian cancer cells. Additionally, the higher CXCR4-expressed cells were highly proliferation after CXCL12 stimulating compared to the CXCR4 non-expressed cells. Next, cancer cells treated with the exogenous activated γ/δ T cells showed a reduction of 35% on cell survival rate. Finally, the combined treatment strategy using AMD3100 plus γ/δ-T cells showed the most significant therapeutic effects in the high-grade ovarian cancer cells, and the cell survival rate was reduced almost to 50% after the cell cytotoxic assay. We therefore conclude that the limitation of CXCL12/CXCR4 activities combined with the γ/δ T cell cytotoxicity is a potent immunotherapy for treating ovarian cancer and would served as a promising new strategies for clinical translation. Citation Format: Chao Lien Liu, Tsui Lien Mao. Immunotherapeutic strategies targeting CXCR4 axis plus γ/δ T cells in treating ovarian cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1679. doi:10.1158