| Autor: |
Cuenca-Micó O; Instituto de Neurobiología, Universidad Nacional Autónoma de México, Querétaro 76230, Mexico., Delgado-González E; Instituto de Neurobiología, Universidad Nacional Autónoma de México, Querétaro 76230, Mexico., Anguiano B; Instituto de Neurobiología, Universidad Nacional Autónoma de México, Querétaro 76230, Mexico., Vaca-Paniagua F; Unidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla 54090, Mexico.; Laboratorio Nacional en Salud, Diagnóstico Molecular y Efecto Ambiental en Enfermedades Crónico Degenerativas, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla 54090, Mexico.; Subdirección de Investigación Básica, Instituto Nacional de Cancerología, Mexico City 14160, Mexico., Medina-Rivera A; Laboratorio Internacional de Investigación sobre el Genoma Humano, UNAM-Juriquilla, Querétaro 76230, Mexico., Rodríguez-Dorantes M; Instituto Nacional de Medicina Genómica, Mexico City 14610, Mexico., Aceves C; Instituto de Neurobiología, Universidad Nacional Autónoma de México, Querétaro 76230, Mexico. |
| Abstrakt: |
Molecular iodine (I 2 ) 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) I 2 supplementation alone (I 2 ) or together with conventional chemotherapy (Cht+I 2 ) on the immune component of breast cancer tumors from a previously published pilot study conducted in Mexico. RNA-seq, I 2 and Cht+I 2 samples showed significant increases in the expression of Th1 and Th17 pathways. Tumor immune composition determined by deconvolution analysis revealed significant increases in M0 macrophages and B lymphocytes in both I 2 groups. Real-time RT-PCR showed that I 2 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+I 2 tumors, GATA3 is silenced ( p = 0.014). Preliminary methylation analysis shows that I 2 activates IFNγ gene promoter (by increasing its unmethylated form) and silences TGFβ in Cht+I 2 . In conclusion, our data showed that I 2 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. |
