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A Micro-Immunotherapy Sequential Medicine MIM-seq Displays Immunomodulatory Effects on Human Macrophages and Anti-Tumor Properties towards In Vitro 2D and 3D Models of Colon Carcinoma and in an In Vivo Subcutaneous Xenograft Colon Carcinoma Model.

Abstract
In this study, the immunomodulatory effects of a sequential micro-immunotherapy medicine, referred as MIM-seq, were appraised in human primary M1 and M2 macrophages, in which the secretion of pro-inflammatory cytokines, such as interleukin (IL)-1β, IL-6, IL-12, IL-23, and tumor necrosis factor (TNF)-alpha, was inhibited. In addition, the potential anti-proliferative effects of MIM-seq on tumor cells was assessed in three models of colorectal cancer (CRC): an in vitro two-dimensions (2D) model of HCT-116 cells, an in vitro tri-dimensional (3D) model of spheroids, and an in vivo model of subcutaneous xenografted mice. In these models, MIM-seq displayed anti-proliferative effects when compared with the vehicle. In vivo, the tumor growth was slightly reduced in MIM-seq-treated animals. Moreover, MIM-seq could slightly reduce the growth of our spheroid models, especially under serum-deprivation. When MIM-seq was combined with two well-known anti-cancerogenic agents, either resveratrol or etoposide, MIM-seq could even further reduce the spheroid's volume, pointing up the need to further assess whether MIM-seq could be beneficial for CRC patients as an adjuvant therapy. Altogether, these data suggest that MIM-seq could have anti-tumor properties against CRC and an immunomodulatory effect towards the mediators of inflammation, whose systemic dysregulation is considered to be a poor prognosis for patients.
AuthorsCamille Jacques, Irene Marchesi, Francesco Paolo Fiorentino, Mathias Chatelais, Nicoletta Libera Lilli, Kurt Appel, Beatrice Lejeune, Ilaria Floris
JournalInternational journal of molecular sciences (Int J Mol Sci) Vol. 23 Issue 11 (May 27 2022) ISSN: 1422-0067 [Electronic] Switzerland
PMID35682738 (Publication Type: Journal Article)
Chemical References
  • Immunologic Factors
  • Tumor Necrosis Factor-alpha
Topics
  • Animals
  • Carcinoma
  • Colonic Neoplasms (drug therapy)
  • Disease Models, Animal
  • Heterografts
  • Humans
  • Immunologic Factors (pharmacology)
  • Immunotherapy
  • Macrophages
  • Mice
  • Tumor Necrosis Factor-alpha (pharmacology)

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