Silencing of Foxp3 delays the growth of murine melanomas and modifies the tumor immunosuppressive environment

Moisés A. Franco-Molina*, Diana F. Miranda-Hernández, Edgar Mendoza-Gamboa, Pablo Zapata-Benavides, Erika E. Coronado-Cerda, Crystel A. Sierra-Rivera, Santiago Saavedra-Alonso, Reyes S. Taméz-Guerra, Cristina Rodríguez-Padilla

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)


Forkhead box p3 (Foxp3) expression was believed to be specific for T-regulatory cells but has recently been described in non-hematopoietic cells from different tissue origins and in tumor cells from both epithelial and non-epithelial tissues. The aim of this study was to elucidate the role of Foxp3 in murine melanoma. The B16F10 cell line Foxp3 silenced with small interference Foxp3 plasmid transfection was established and named B16F10.1. These cells had lower levels of Foxp3 mRNA (quantitative real-time reverse transcription-polymerase chain reaction [0.235-fold]), protein (flow cytometry [0.02%]), CD25 + expression (0.06%), cellular proliferation (trypan blue staining), and interleukin (IL)-2 production (enzyme-linked immunosorbent assay [72.35 pg/mL]) than those in B16F10 wild-type (WT) cells (P<0.05). Subcutaneous inoculation of the B16F10.1 cell line into C57BL/6 mice delayed the time of visible tumor appearance, increased the time of survival, and affected the weight of tumors, and also decreased the production of IL-10, IL-2, and transforming growth factor beta compared with mice inoculated with the B16F10 WT cell line. The B16F10.1 cells derived from tumors and free of T-cells (isolated by Dynabeads and plastic attachment) expressed relatively lower levels of Foxp3 and CD25 + than B16F10 WT cells (P<0.05) in a time-dependent manner. The population of tumor-infiltrating lymphocytes of T CD4+ cells (CD4 +, CD4 +CD25 +, and CD4 +CD25 +Foxp3 +) increased in a time-dependent manner (P<0.05) in tumors derived from B16F10 WT cells and decreased in tumors derived from B16F10.1 cells. Similar data were obtained from spleen cells. These results suggest that, in melanomas, Foxp3 partly induces tumor growth by modifying the immune system at the local and peripheral level, shifting the environment toward an immunosuppressive profile. Therapies incorporating this transcription factor could be strategies for cancer treatment.

Original languageEnglish
Pages (from-to)243-253
Number of pages11
JournalOncoTargets and Therapy
Issue number9
Publication statusPublished - 12 Jan 2016
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2016 Franco-Molina et al.

All Science Journal Classification (ASJC) codes

  • Oncology
  • Pharmacology (medical)


Dive into the research topics of 'Silencing of Foxp3 delays the growth of murine melanomas and modifies the tumor immunosuppressive environment'. Together they form a unique fingerprint.

Cite this