[go: up one dir, main page]
More Web Proxy on the site http://driver.im/

IKZF1 Enhances Immune Infiltrate Recruitment in Solid Tumors and Susceptibility to Immunotherapy

Cell Syst. 2018 Jul 25;7(1):92-103.e4. doi: 10.1016/j.cels.2018.05.020. Epub 2018 Jun 27.

Abstract

Immunotherapies are some of the most promising emergent treatments for several cancers, yet there remains a majority of patients who do not benefit from them due to immune-resistant tumors. One avenue for enhancing treatment for these patients is by converting these tumors to an immunoreactive state, thereby restoring treatment efficacy. By leveraging regulatory networks we previously characterized in autoimmunity, here we show that overexpression of the master regulator IKZF1 leads to enhanced immune infiltrate recruitment and tumor sensitivity to PD1 and CTLA4 inhibitors in several tumors that normally lack IKZF1 expression. This work provides proof of concept that tumors can be rendered susceptible by hijacking immune cell recruitment signals through molecular master regulators. On a broader scale, this work also demonstrates the feasibility of using computational approaches to drive the discovery of novel molecular mechanisms toward treatment.

Keywords: cancer genetics; immune checkpoint; immune evasion; immuno-oncology; inhibitors; precision medicine; regulatory networks; systems biology.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antibodies, Monoclonal / metabolism
  • Antibodies, Monoclonal / pharmacology*
  • CTLA-4 Antigen / immunology
  • Cell Line, Tumor
  • Female
  • Humans
  • Ikaros Transcription Factor / metabolism*
  • Ikaros Transcription Factor / physiology
  • Immunologic Factors
  • Immunotherapy / methods
  • Mice
  • Mice, Inbred C57BL
  • Mice, Nude
  • Neoplasms / immunology*
  • Programmed Cell Death 1 Receptor / immunology
  • Systems Biology / methods

Substances

  • Antibodies, Monoclonal
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • IKZF1 protein, human
  • Immunologic Factors
  • Programmed Cell Death 1 Receptor
  • Ikaros Transcription Factor