Peripheral Blood Cytokines Levels in Senegalese Women with Cervical Cancer during Chemotherapy

Abstract

Cervical cancer is the leading cause of cancer deaths of women in developing world. Several studies demonstrated evidences of inflammatory cytokines implication in cancer progression including in initiation, promotion and invasion by affecting the immune surveillance. Our aim was to measure blood circulating pro- and anti-inflammatory cytokines levels, their profiles according to treatment issue and relation with prognostic factors in cervical cancer during chemotherapy. Blood samples were collected from a cohort of 35 cervical cancer women and 42 women healthy controls (HC) with no history of malignancy. For each CP, three samples were taken at three-week intervals. The first one (S1) was taken before initiation of the chemotherapy protocol. S2 and S3 were samples collected respectively at day 21 and day 42. Cytokines levels were evaluated by ELISA. Mean age of patients was 54.1 year (35 - 77 yo). In groups, no relation was observed between age and cytokines levels. Before chemotherapy, high levels of IL-6, IL-4 and IFN-γ were observed in CP compared to HC (p 0.001) and at the same period, IL-10 and TNF-α levels were significantly low in CP (p 0.05) and negatively correlated (r = —0.79; p = 0.017). In this CP group, IL-4 levels were positively correlated between S1 and S2 (r = 0.72; p = 0.002) and between S1 and S3 (r = 0.74; p = 0.019). Similar correlations were observed for TNF-α levels: S1/S2 (r = 0.54; p = 0.027), S2/S3 (r = 0.82; p = 0.009) and S1/S3 (r = 0.66; p = 0.036) with a significant increase of TNF-α in blood during treatment. Depending on chemotherapy’s efficacy, CP patients were separated into 1) non responders (NR), 2) partial responders (PR) and 3) good responders (GR). Compared to PR and GR groups, NR patients showed: a) higher serum levels of IL-6, IL-10 and IFN-γ during the follow-up and b) lower serum levels of IL-4 and TNF-α. In addition, serum levels of IL-4 were significantly higher in GR patients however TNF-α was the predominant cytokines in PR group. Our results highlight the variation of circulating cytokines such as IL-6, IL-10 and IFN-γ during cervical cancer chemotherapy. In addition, this study suggested that IL-4 and TNF-α might represent potential biomarkers candidate in cervical cancer. Applications in cancer management need further investigations particularly about the relevant prognostic indicator following chemotherapy and validation studies must provide more assurance for translation into clinical practice.