Targeting immune suppressing myeloid-derived suppressor cells in oncology

Johnny Kao, Eric C. Ko, Samuel Eisenstein, Andrew G. Sikora, Shibo Fu, Shu hsia Chen

Research output: Contribution to journalReview articlepeer-review

126 Scopus citations

Abstract

Emerging data suggests that host immune cells with a suppressive phenotype represent a significant hurdle to successful therapy for metastatic cancer. Among the suppressor cells, T regulatory cells (Treg) and myeloid-derived suppressor cells (MDSC) are significantly increased in hosts with advanced malignancies. MDSC mediate the suppression of the tumor antigen-specific T cell response through the induction of T cell anergy and the development of Treg in tumor-bearing mice. These results provide robust evidence of an in vivo immunoregulatory function of MDSC in the establishment of tumor antigen-specific tolerance and the development of Treg in tumor-bearing hosts. To achieve effective anti-tumor immunity, tumor-induced immunosuppression must be reversed. Our preliminary results indicate that c-kit ligand (stem cell factor) expressed by tumor cells may be required for MDSC accumulation in tumor-bearing mice, and that blocking the c-kit ligand/c-kit receptor interaction can prevent the development of Treg and reverse immune tolerance induced by MDSC. Since c-kit can be readily inhibited by several small molecule inhibitors including imatinib, sunitinib and dasatinib, targeting immune suppressing cells can be readily accomplished in the clinic.

Original languageEnglish
Pages (from-to)12-19
Number of pages8
JournalCritical Reviews in Oncology/Hematology
Volume77
Issue number1
DOIs
StatePublished - Jan 2011

Keywords

  • Myeloid-derived suppressor cells
  • Radiation therapy
  • Stem cell factor (c-kit)
  • Sunitinib
  • T regulatory cells
  • Tumor immunotherapy

Fingerprint

Dive into the research topics of 'Targeting immune suppressing myeloid-derived suppressor cells in oncology'. Together they form a unique fingerprint.

Cite this