Beneficial Effect of Toxoplasma gondii Infection on the Prognosis of Breast Cancer Was Modified by Cytokines

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

Data Sharing Statement

The datasets used and analyzed during this study were available from the corresponding author on request.

Ethics Approval and Informed Consent

This study was approved by the Ethics Committee of the School of Public Health at Sun Yat-sen University (number of Institutional Review Board approval: 2012-8) and performed in accordance with the Declaration of Helsinki. The written informed consents were obtained from all the participants.

Consent for Publication

Written informed consent for publication was obtained from all participants.

Acknowledgments

We sincerely thank the patients who participated in this study, the staff who conducted the baseline and the follow‐up data collection, and the medical staff in the breast departments of the First Affiliated Hospital, the Second Affiliated Hospital, and the Cancer Center of Sun Yat‐Sen University.

Author Contributions

All authors contributed to study design, data collection, statistical analysis and interpretation, visualization, drafting or revising the article; have agreed on the journal to which the article will be submitted, gave final approval of the version to be published, and agreed to be accountable for all aspects of the work.

Disclosure

The authors declare that they have no competing interests.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China [Grant Numbers 81973115] and the Science and Technology Planning Project of Guangdong Province, China [Grant Number 2019B030316002].