Occupational exposure to pesticides dysregulates systemic Th1/Th2/Th17 cytokines and correlates with poor clinical outcomes in breast cancer patients

Front Immunol. 2023 Oct 24:14:1281056. doi: 10.3389/fimmu.2023.1281056. eCollection 2023.

Abstract

Pesticides are compounds known to cause immunetoxicity in exposed individuals, which have a potential to substantially modify the prognosis of pathologies dependent on an efficient immune response, such as breast cancer. In this context, we examined the circulating cytokine profile of Th1/Th2/Th17 patterns in women occupationally exposed to pesticides and their correlation with worse prognostic outcomes. Peripheral blood samples were collected from 187 rural working women with breast cancer, occupationally exposed or not to pesticides, to quantify the levels of cytokines IL-1β, IL-12, IL-4, IL-17-A, and TNF -α. Data on the disease profile and clinical outcomes were collected through medical follow-up. IL-12 was reduced in exposed women with tumors larger than 2 cm and in those with lymph node metastases. Significantly reduced levels of IL-17A were observed in exposed patients with Luminal B subtype tumors, with high ki67 proliferation rates, high histological grade, and positive for the progesterone receptor. Reduced IL-4 was also seen in exposed women with lymph node invasion. Our data show that occupational exposure to pesticides induces significant changes in the levels of cytokines necessary for tumor control and correlates with poor prognosis clinical outcomes in breast cancer.

Keywords: breast cancer; cytokines; dysregulation; immune response; prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms* / pathology
  • Cytokines
  • Female
  • Humans
  • Interleukin-12
  • Interleukin-4
  • Occupational Exposure* / adverse effects
  • Pesticides* / adverse effects
  • Tumor Necrosis Factor-alpha

Substances

  • Cytokines
  • Pesticides
  • Interleukin-4
  • Tumor Necrosis Factor-alpha
  • Interleukin-12

Grants and funding

This work was supported in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (CAPES), Fundação Araucária, Programa de Pesquisa Para o SUS – PPSUS, Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, Edital Universal). The authors are grateful for all Lab and Hospital personnel, funding agencies and patients. Carolina Panis was supported by CNPq Grants 402364/2021-0 and 305335/2021-9.