IFNγ-IL-17-IL-22+CD4+ subset and IL-22-producing cells in tumor draining lymph nodes of patients with breast cancer

Article type: Research Article

Authors: Salmanpour, Ali^a | Rezaeifard, Somayeh^a | Kiani, Razie^a | Tahmasebi, Sedigheh^{b; c} | Faghih, Zahra^a; | Erfani, Nasrollah^{a; d;}

Affiliations: [a] Cancer Immunology and Immunotherapy Group, Shiraz Institute for Cancer Research, Shiraz University of Medical Sciences, Shiraz, Iran | [b] Department of Surgery, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran | [c] Breast Disease Research Center, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran | [d] Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

Correspondence: [*] Corresponding author: Nasrollah Erfani, PhD, Department of Immunology, School of Medicicn, Shiraz University of Medical Scineces, Shiraz, P.O. Box: 71345-1798, Iran. Tel.:/Fax: (+98 71) 3235 1557; E-mail: [email protected]

Note: [†] Correspondences could also be referred to: Zahra Faghih, PhD, Cancer Immunology and Immunotherapy Group, Shiraz Institute for Cancer Research, Shiraz University of Medical Sciences, Shiraz, Iran. E-mail: [email protected]

Abstract: BACKGROUND:A recently introduced CD4+ T subset that mainly secretes interleukin (IL-) 22 has been reported to be associated with a variety of tumors, including colon, gastric, hepatocellular, and small- and large-cell lung carcinoma. Both tumor-promoting and - suppressing roles have been suggested for these cells. In the present study, we aimed to investigate the frequency of IL-22-producing subsets in tumor-draining lymph nodes (TDLNs) of the patients with breast cancer and determine their association with the clinicopathological characterizations of the disease. METHODS:Thirty untreated women diagnosed with breast cancer were enrolled and their axillary lymph nodes were dissected during surgery. Mononuclear cells were isolated using Ficoll density gradient, activated, permeabilized, and stained by fluorochrome-conjugated antibodies against CD4, IL-22, IL-17, and IFNγ. The cells were then acquired on the FACSCalibur flow cytometer, and raw data was analyzed by the FlowJo software package (V10). RESULTS:Our results demonstrated that 2.39% ± 0.39 of CD4+ lymphocytes in TDLNs of patients with breast cancer produced IL-22. Among them, 0.64% ± 0.8 just produced IL-22 but were negative for IFNγ and IL-17. Statistical analysis indicated that the frequency of CD4+IL-22+ cells was significantly higher in the patients with stage III and the ones with 3–9 tumor involved lymph nodes (N2) compared to those with stage II and those having 1–3 tumor involved lymph nodes (N1) (P = 0.008 and P = 0.004, respectively). CONCLUSION:The higher frequency of IL-22-producing cells in draining lymph nodes of patients with more advanced tumors (higher stage (stage III) and more involved lymph nodes) suggests a role for IL-22-producing cells in the tumor progression and invasion. However, further studies with larger sample size and more functional studies are needed to clarify the role of IL-22-producing cells in breast cancer pathogenesis.

Keywords: Breast cancer, lymph nodes, T helper 22, IL-22-producing cells

DOI: 10.3233/BD-210084

Journal: Breast Disease, vol. 41, no. 1, pp. 383-390, 2022