High OX40 expression in recurrent ovarian carcinoma is indicative for response to repeated chemotherapy

Abstract

BackgroundOvarian carcinoma (OC) is the fifth most common female cancer and mostly diagnosed at an advanced stage. Surgical debulking is usually followed by adjuvant platinum-based chemotherapy. Only few biomarkers are known to be related to chemosensitivity. OX40 is a TNF receptor member and expressed on activated CD4+ and CD8+ T cells. It is known that OX40 signaling promotes survival and responds to various immune cells of the innate and adaptive immune system. Therefore we investigated the indicative value of OX40 expression for recurrence and survival in OC.MethodsA tissue microarray of biopsies of mostly high-grade primary serous OC and matched recurrences of 47 patients was stained with OX40. Recurrence within 6 months of the completion of platinum-based chemotherapy was defined as chemoresistance.ResultsChemosensitivity correlated significantly with high OX40 positive immune cell density in primary cancer biopsies (p = 0.027). Furthermore patients with a higher OX40 expression in recurrent cancer biopsies showed a better outcome in recurrence free survival (RFS) (p = 0.017) and high OX40 expression was associated with chemosensitivity (p = 0.008). OX40 positive TICI in recurrent carcinomas significantly correlated with IL-17 positive tumor infiltrating immune cells in primary carcinomas (rs = 0.34; p = 0.023). Univariate cox regression analysis revealed a significant longer RFS and higher numbers of chemotherapy cycles for high OX40 tumor cell expression in recurrent cancer biopsies (HR 0.39, 95%CI 0.16–0.94, p = 0.036 and 1.28, 95%CI 1.05–1.55; p = 0.013).ConclusionHigh OX40 expression in OC is correlated with chemosensitivity and improved RFS in OC. Patients might therefore benefit from a second line therapy.

OX40 and OX40L protein expression of tumor infiltrating lymphocytes in non-small cell lung cancer and its role in clinical outcome and relationships with other immune biomarkers

“…To our knowledge, it is the first research to analyze the role of OX40/OX40L in early-stage resectable NSCLC and demonstrate its relationships with PD-1/PD-L1, TILs and patients' clinical outcomes. OX40/OX40L has already been studied previously as an immune characteristic biomarker in some other cancer types, including lymphoma, hepatocellular carcinoma, Leukemia, ovarian, neuroblastoma, head and neck squamous cell carcinoma, gastric cancer and breast cancer (52)(53)(54)(55)(56)(57)(58)(59)(60)(61)(62)(63). The TILs OX40 was reported to correlate with patient survival.…”

Antiproliferative Effects of Alkaloid Evodiamine and Its Derivatives

“…Ovarian cancer is another common gynecological tumor, and >70% of patients ultimately die from the disease [ 72 , 73 ]. Chen et al (2016) evaluate the cytotoxic activities of evodiamine in human epithelial ovarian cancer cell lines ES-2, SKOV-3, A2780, and A2780CP.…”

New pathways in immune stimulation: targeting OX40

“…Ramser et al analysed the positivity for OX40+infiltrating immune cells and tumour tissue from biopsies of primary and recurrent stages III and IV ovarian cancer (OC) in humans 33. Chemosensitivity was associated with high expression of OX40 on immune cells for primary OC and on tumour cells in recurrent OC; the patients who were OX40 negative in immune and tumour cells had the worse recurrence-free survival.…”