High OX40 expression in recurrent ovarian carcinoma is indicative for response to repeated chemotherapy
Autor: | Sylvia Stadlmann, Gad Singer, Athanasios Tampakis, Marko Kraljević, Robert Mechera, Benjamin Weixler, Tarik Delko, Raoul A. Droeser, Simone Eichelberger, Luigi Terracciano, Uwe Güth, Michaela Ramser, Silvio Däster |
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Rok vydání: | 2018 |
Předmět: |
Adult
0301 basic medicine Oncology Cancer Research medicine.medical_specialty Drug-Related Side Effects and Adverse Reactions OX40 Ligand lcsh:RC254-282 Disease-Free Survival 03 medical and health sciences 0302 clinical medicine Drug Therapy Ovarian cancer Surgical oncology CD134 Internal medicine Biomarkers Tumor Genetics Humans Medicine OX40 Chemosensitivity Aged Neoplasm Staging Ovarian Neoplasms Tissue microarray business.industry Carcinoma Cancer Middle Aged lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Prognosis medicine.disease Debulking Gene Expression Regulation Neoplastic Serous fluid 030104 developmental biology 030220 oncology & carcinogenesis Female business Recurrent Ovarian Carcinoma Research Article |
Zdroj: | BMC Cancer BMC Cancer, Vol 18, Iss 1, Pp 1-9 (2018) |
ISSN: | 1471-2407 |
Popis: | Background Ovarian 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. Methods A 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. Results Chemosensitivity 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 (r s = 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). Conclusion High OX40 expression in OC is correlated with chemosensitivity and improved RFS in OC. Patients might therefore benefit from a second line therapy. |
Databáze: | OpenAIRE |
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