Cytokines and Prognostic Factors in Epithelial Ovarian Cancer

Abstract

INTRODUCTIONOvarian cancer has a high mortality and delayed diagnosis. Inflammation is a risk factor for ovarian cancer, and the inflammatory response is involved in almost all stages of tumor development. Immunohistochemical staining in stroma and epithelium of a panel of cytokines in benign and malignant ovarian neoplasm was evaluated. In addition, immunostaining was related to prognostic factors in malignant tumors.METHODThe study group comprised 28 ovarian benign neoplasias and 28 ovarian malignant neoplasms. A panel of cytokines was evaluated by immunohistochemistry (Th1: IL-2 and IL-8; Th2: IL-5, IL-6, and IL-10; and TNFR1). Chi-square test with Yates’ correction was used, which was considered significant if less than 0.05.RESULTSTNFR1, IL-5, and IL-10 had more frequent immunostaining 2/3 in benign neoplasms compared with malignant tumors. Malignant tumors had more frequent immunostaining 2/3 for IL-2 in relation to benign tumors. The immunostaining 0/1 of IL 8 was more frequent in the stroma of benign neoplasms compared with malignant neoplasms. Evaluation of the ovarian cancer stroma showed that histological grade 3 was significantly correlated with staining 2/3 for IL-2 (P = 0.004). Women whose disease-free survival was less than 2.5 years had TNFR1 stromal staining 2/3 (P = 0.03) more frequently.CONCLUSIONIL-2 and TNFR1 stromal immunostaining are related prognostic factors in ovarian cancer and can be the target of new therapeutic strategies.

Anti-inflammatory Effects of Cardamonin in Ovarian Cancer Cells Are Mediated via mTOR Suppression

“…Inflammatory factors play important roles in the development of ovarian cancer [38,39]. In this study, cardamonin and rapamycin inhibited the expression of TNF-α and IL-6 under both conditions.…”

The Crosstalk between Ovarian Cancer Stem Cell Niche and the Tumor Microenvironment

“…In the case of ovarian cancer, it is known that an inflammatory state is considered a risk factor and can be associated with ovarian cancer development, drug resistance, and metastasis [ 31 , 32 ]. Several cytokines have been described in circulation, ascites, and cyst fluid of patients with ovarian cancer [ 33 – 38 ] and also in the stroma and epithelium of tumors [ 39 ]. The presence of cytokines in the tumor stroma raises the possibility of activating signaling pathways related to the inflammatory network in all cell types of the stroma, including the ovarian CSCs.…”

Role of tumor microenvironment in the pathobiology of ovarian cancer: Insights and therapeutic opportunities

“…Increased TAMs not only promotes cancer cell invasiveness but also contributes to immunosuppressive environment suppressing T cells, dendritic (DCs) and natural killer (NK) cells functions . TAMs also contribute to the phenotypic switch of fibroblasts into CAFs, and in turn activate multiple pathways that lead to chemoresistance, recurrence, and poor prognosis . The augmented inflammatory TME promoted clinical trials targeting inflammatory cytokines/chemokines and their receptors, as well as COX‐2 inhibitors (Table ). Myeloid‐derived Suppressor Cells ( MDSCs ) are heterogeneous population of myeloid cells that, in the immature state, are present in the bone marrow and lack suppressive activity.…”

“…8 TAMs also contribute to the phenotypic switch of fibroblasts into CAFs, and in turn activate multiple pathways that lead to chemoresistance, recurrence, and poor prognosis. 63,64 The augmented inflammatory TME promoted clinical trials targeting inflammatory cytokines/chemokines and their receptors, as well as COX-2 inhibitors ( targeting CXCR4 in OvCa therapy 66 (Table 1). Increased MDSCs in the OvCa TME also maintain OvCa stem cells phenotype.…”