Sulconazole inhibits PD-1 expression in immune cells and cancer cells malignant phenotype through NF-κB and calcium activity repression.

The overexpression of the immunoinhibitory receptor programmed death-1 (PD1) on T-cells is involved in immune evasion in cancer. The use of anti-PD-1/PDL-1 strategy has deeply changed the therapies of cancers and patient survival. However, their efficacy diverges greatly along with tumor type and patient populations. Thereby, novel treatments are needed to interfere with the anti-tumoral immune responses and propose an adjunct therapy. In the current study, we found that the antifungal drug Sulconazole (SCZ) inhibits PD-1 expression on activated PBMCs and T cells at the RNA and protein levels. SCZ repressed NF-κB and calcium signaling, both, involved in the induction of PD-1. Further analysis revealed cancer cells treatment with SCZ inhibited their proliferation, and migration and ability to mediate tumor growth in zebrafish embryos. SCZ found also to inhibit calcium mobilization in cancer cells. These results suggest the SCZ therapeutic potential used alone or as adjunct strategy to prevent T-cell exhaustion and promotes cancer cell malignant phenotype repression in order to improve tumor eradication.

La regulación epigenética en la línea germinal / Epigenetic regulation in the germ line

La manipulación de la secuencia genética de la línea germinal con las actuales técnicas genera un gran rechazo por la falta de especificidad y seguridad, por un lado, y, por otro lado, por la acción directa que se ejerce sobre la secuencia de bases de la que se compone el genoma humano. La epigenética nos brinda la posibilidad de actuar sobre la expresión génica sin alterar la secuencia, una opción plausible que evita ciertas confrontaciones bioéticas. Los conocimientos que se van adquiriendo en este campo y su posible uso en nuevas aproximaciones terapéuticas abre un nuevo debate.(AU)

The manipulation of the genetic sequence of the germ line with current techniques generates great rejection due to the lack of specificity and safety, on the one hand, and, on the other hand, due to the direct action exerted on the sequence of bases of which the human genome is composed. Epigenetics offers us the possibility of acting on gene expression without altering the sequence, a plausible option that avoids certain bioethical confrontations. The knowledge that is being acquired in this field and its possible use in new therapeutic approaches opens up a new debate.(AU)