Effects of Molecular Iodine/Chemotherapy in the Immune Component of Breast Cancer Tumoral Microenvironment

• DOI: 10.20944/preprints202109.0170.v1
• Publication Date: 2021-09-10T07:25:38Z
• Authors: Olga Cuenca-Micó; Evangelina Delgad...; Brenda Anguiano; Felipe Vaca-Paniagua; Alejandra Medina-...; Mauricio Rodrígue...; Carmen Aceves
• Keywords: Adult; 0301 basic medicine; Angiogenesis Inhibitors; Apoptosis; Breast Neoplasms; GATA3 Transcription Factor; Microbiology; immune response; Article; Transforming Growth Factor beta1; Interferon-gamma; 03 medical and health sciences; breast cancer; Humans; RNA-Seq; Mexico; oncology_oncogenics; Aged; Cell Proliferation; B-Lymphocytes; 0303 health sciences; molecular iodine; Macrophages; Immunity; Middle Aged; Th1 Cells; QR1-502; 3. Good health; Th17 Cells; Female; Iodine

Molecular iodine (I2) induces apoptotic, antiangiogenic, and antiproliferative effects in breast cancer cells. Little is known about its effects on the tumor immune microenvironment. We studied the effect of oral (5 mg/day) I2 supplementation alone (I2) or together with conventional chemotherapy (Cht+I2) on the im-mune component of breast cancer tumors from a previously published pilot study conducted in Mexico. RNA-seq, I2 and Cht+I2 samples showed significant increases in expression of Th1 and Th17 pathways. Tumor immune composition determined by deconvolution analysis revealed significant increases in M0 macrophages and B lymphocytes in both I2 groups. Real-time RT-PCR showed that I2 tumors overexpress T-BET (p = 0.019) and interferon-gamma (IFNγ; p = 0.020) and silence tumor growth factor-beta (TGFβ; p = 0.049); whereas in Cht+I2 tumors, GATA3 is silenced (p = 0.014). Preliminary methylation analysis shows that I2 activates IFNγ gene promoter (by increasing its unmethylated form) and silences TGFβ in Cht+I2. In conclusion, our data showed that I2 supplements induce the activation of the immune response and that when combined with Cht, the Th1 pathways are stimulated. The molecular mechanisms involved in these responses are being analyzed, but preliminary data suggest that methylation/demethylation mechanisms could also participate.