Beneficial Effect of Toxoplasma gondii Infection on the Prognosis of Breast Cancer Was Modified by Cytokines
Hengming Ye, Min-Jie Lu, Qiang Liu, Ying Lin, Lu-Ying Tang, Zefang Ren
Abstract
Background: Animal experiments have shown the anticancer activity of Toxoplasma gondii ( T. gondii ), but its effect on the prognosis of cancer patients is unclear. Thus, the present study aimed to investigate the prognostic role of anti- T. gondii IgG in breast cancer patients and the modification effect of cytokines. Methods: A total of 1121 breast cancer patients were recruited between 2008 and 2018 and followed up until December 31, 2021. Anti- T. gondii IgG and cytokines were measured using an enzyme-linked immunosorbent assay (ELISA) kit and a multiplex assay platform. Endpoints were overall survival (OS) and progression-free survival (PFS). Survival and multiplicative interaction analyses were performed using multivariate Cox regression models. Results: According to the cutoff value of optical density (OD=0.111), 900 (80.29%) and 221 (19.71%) patients were divided into two groups: low or high anti- T. gondii IgG. Compared to patients with a low anti- T. gondii IgG level, the adjusted hazard ratios (HRs) of OS and PFS for patients with high anti- T. gondii IgG levels were 0.60 (95% confidence interval (CI): 0.37– 0.99) and 0.67 (0.46– 0.98), respectively. These associations were profound among patients with a high cytokine score (HR=0.29, 95% CI: 0.10– 0.82 for OS; HR=0.30, 95% CI: 0.13– 0.69 for PFS), accompanied by a significant interaction between the level of anti- T. gondii IgG and the cytokine score ( P interaction =0.019 for PFS); interleukin-17 (IL-17) and interleukin-9 (IL-9) were the main contributors to the interaction. Conclusion: Anti- T. gondii IgG was found to be beneficial to breast cancer survival, especially in women with systematic inflammation and high IL-17 or IL-9 levels, suggesting the potential of T. gondii as a prognostic marker and a novel immunotherapy approach for cancer patients. Keywords: Toxoplasma gondii , breast cancer, prognosis, cytokines