Targeting CC-chemokine receptor type 1 (CCR1) in pre-clinical cancer models has shown reduction in tumor burden. Similar agents have also been safely used in clinical trials for autoimmune conditions. Despite promising results in cancer models and adequate safety profiles, the role of targeting CCR1 in ovarian cancer is poorly understood, warranting further evaluation. We have identified a macrophage-driven chemokine receptor axis, CCL23/CCR1 that may play a critical role in ovarian cancer metastasis. We hypothesize that CCR1 expressed by ovarian cancer cells and the differential expression of this chemokine receptor may have a prognostic role in survival and response to chemotherapy. We performed immunofluorescence and immunohistochemistry to profile the expression of CCR1 in a cell array containing 53 ovarian cancer cell lines and in three tissue microarrays containing greater than 1000 cores from 192 patients diagnosed with serous, endometrioid, or clear cell ovarian carcinoma. We measured the percent of CCR1 3,3′-Diaminobenzidine (DAB) staining using HALO image analysis software’s area quantification algorithm (Indica Labs, Corrales, NM) and correlated with survival. We analyzed three tissue microarrays containing varied histologic subtypes of ovarian cancer and found that CCR1 was highly expressed, defined as greater than 30% DAB staining, in 53% of serous (N=93), 68% of endometrioid (N=66), and 45% of clear cell carcinoma (N=22) averaged tissue cores. In comparing different ovarian cancer histologic subtypes, averaged tissue cores from patients with endometrioid carcinoma have significantly higher expression of CCR1, compared to serous carcinoma and clear cell carcinoma, 10.5% (p≤0.02) and 12.5% (p≤0.002), respectively. In all histotypes, we observed a significant lower median progression-free survival (p≤0.05) in patients with high CCR1 expression. Interestingly, in evaluating the level of CCR1 expression and response to platinum chemotherapy, we found that patients with platinum resistance (N=36) (defined as recurrence after 12 months of completing chemotherapy) had significantly higher expression of CCR1 compared to patients that were platinum sensitive (N=92) (p≤0.04). In addition, we analyzed a cell array and found differential expression of CCR1 across phenotypically different lines. For example, the cell lines OVCA420, OVSAHO, and OVCAR3 showed higher expression of CCR1 compared to TOV-21G, MOVCAR18, and OVCAR5. Given the potential prognostic significance of CCR1 in ovarian cancer, our future studies are focused on determining the functional role of CCR1 inhibition using both in vitro migration and in vivo colonization assays. Outcomes from pre-clinical studies will inform us on the clinical translatability for targeting CCR1 in patients with epithelial ovarian cancer.

Citation Format: Anita M. Chanana, Venkatesh Krishnan, Supreeti Tallapragada, Oliver Dorigo. C-C chemokine receptor type 1 is a prognostic indicator in ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1964.