Aptamer-mediated blockade of IL4Rα triggers apoptosis of MDSCs and limits tumor progression

Felix Roth, Adriana C. De La Fuente, Jennifer L. Vella, Alessia Zoso, Luca A Inverardi, Paolo Serafini

Research output: Contribution to journalArticle

102 Citations (Scopus)

Abstract

In addition to promoting tumor progression and metastasis by enhancing angiogenesis and invasion, myeloid-derived suppressor cells (MDSC) and tumor-associated macrophage (TAM) also inhibit antitumor T-cell functions and limit the efficacy of immunotherapeutic interventions. Despite the importance of these leukocyte populations, a simple method for their specific depletion has not been developed. In this study, we generated an RNA aptamer that blocks the murine or human IL-4 receptor-α (IL4Rα or CD124) that is critical for MDSC suppression function. In tumor-bearing mice, this anti-IL4Rα aptamer preferentially targeted MDSCs and TAM and unexpectedly promoted their elimination, an effect that was associated with an increased number of tumor-infiltrating T cells and a reduction in tumor growth. Mechanistic investigations of aptamer-triggered apoptosis in MDSCs confirmed the importance of IL4Ra-STAT6 pathway activation in MDSC survival. Our findings define a straightforward strategy to deplete MDSCs and TAMs in vivo, and they strengthen the concept that IL4Rαsignaling is pivotal for MDSC survival. More broadly, these findings suggest therapeutic strategies based on IL4Rα signaling blockades to arrest an important cellular mechanism of tumoral immune escape mediated by MDSCs and TAM in cancer.

Original languageEnglish
Pages (from-to)1373-1383
Number of pages11
JournalCancer Research
Volume72
Issue number6
DOIs
StatePublished - Mar 15 2012

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Apoptosis
Neoplasms
Macrophages
Cell Survival
Interleukin-4 Receptors
Nucleotide Aptamers
T-Lymphocytes
Myeloid-Derived Suppressor Cells
Leukocytes
Neoplasm Metastasis
Growth
Population

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Aptamer-mediated blockade of IL4Rα triggers apoptosis of MDSCs and limits tumor progression. / Roth, Felix; De La Fuente, Adriana C.; Vella, Jennifer L.; Zoso, Alessia; Inverardi, Luca A; Serafini, Paolo.

In: Cancer Research, Vol. 72, No. 6, 15.03.2012, p. 1373-1383.

Research output: Contribution to journalArticle

Roth, Felix ; De La Fuente, Adriana C. ; Vella, Jennifer L. ; Zoso, Alessia ; Inverardi, Luca A ; Serafini, Paolo. / Aptamer-mediated blockade of IL4Rα triggers apoptosis of MDSCs and limits tumor progression. In: Cancer Research. 2012 ; Vol. 72, No. 6. pp. 1373-1383.
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