Role of Aiolos and Ikaros in the Antitumor and Immunomodulatory Activity of IMiDs in Multiple Myeloma: Better to Lose Than to Find Them

Marco Cippitelli, Helena Stabile, Andrea Kosta, Sara Petillo, Angela Gismondi, Angela Santoni, Cinzia Fionda

Research output: Contribution to journalReview articlepeer-review

Abstract

The Ikaros zing-finger family transcription factors (IKZF TFs) are important regulators of lymphocyte development and differentiation and are also highly expressed in B cell malignancies, including Multiple Myeloma (MM), where they are required for cancer cell growth and survival. Moreover, IKZF TFs negatively control the functional properties of many immune cells. Thus, the targeting of these proteins has relevant therapeutic implications in cancer. Indeed, accumulating evidence demonstrated that downregulation of Ikaros and Aiolos, two members of the IKZF family, in malignant plasma cells as well as in adaptative and innate lymphocytes, is key for the anti-myeloma activity of Immunomodulatory drugs (IMiDs). This review is focused on IKZF TF-related pathways in MM. In particular, we will address how the depletion of IKZF TFs exerts cytotoxic effects on MM cells, by reducing their survival and proliferation, and concomitantly potentiates the antitumor immune response, thus contributing to therapeutic efficacy of IMiDs, a cornerstone in the treatment of this neoplasia.

Original languageEnglish
JournalInt J Mol Sci
Volume22
Issue number3
DOIs
Publication statusPublished - Jan 22 2021

Keywords

  • Animals
  • Antineoplastic Agents/pharmacology
  • Apoptosis/drug effects
  • Cell Differentiation/drug effects
  • Cell Line, Tumor
  • Cell Proliferation
  • Cell Survival
  • Humans
  • Ikaros Transcription Factor/genetics
  • Immunity/drug effects
  • Immunomodulation/drug effects
  • Lenalidomide/pharmacology
  • Lymphocytes/cytology
  • Mice
  • Multiple Myeloma/drug therapy
  • Thalidomide/pharmacology

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