Abstract Resistance to platinum-based chemotherapy remains a major impediment in the treatment of serous epithelial ovarian cancer. Recent studies have drawn attention to the role of the tumor-microenvironment in mediating chemotherapy resistance, in addition to established mechanisms of tumor progression. This project is investigating the role of the tumor inflammatory microenvironment in facilitating intrinsic chemotherapy resistance using a cohort of 36 high-grade serous epithelial ovarian cancer patient tumor samples. Total RNA from forty-eight, HGSEOC tumor tissue samples was subjected to gene expression profiling using NanoString technology. This type of bar-coded expression profiling has proven to be equally efficient to study gene expression as quantitative real time PCR technique. The gene panel consisted of 184 human genes that are differentially expressed in human inflammation and 6 internal reference genes. The cohort comprised 18 sensitive (PFS >18months) and 18 resistant (PFS<6 months) samples. A multiplex cytokine assay using the bioplex system was also performed on serum samples from a subset of this cohort. The results showed significant differences in expression of some inflammatory cytokines in the serum that were concurrent with the observed gene expression differences in the tumor samples. The results are indicative of a cooperative role of a specific inflammatory gene signature within the tumor microenvironment that may augment pathways leading to differential drug response. These studies need further independent validations to derive non-invasive blood-based biomarkers for use in predicting chemotherapy resistance in serous epithelial ovarian cancer. Citation Format: Madhuri Koti, Andrew Edwards, Jeremy A. Squire. The tumor immune microenvironment modulates response to chemotherapy in high-grade serous epithelial ovarian cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1106. doi:10.1158/1538-7445.AM2014-1106