Targeted STAT3 disruption in myeloid cells alters immunosuppressor cell abundance in a murine model of spontaneous medulloblastoma

Catalina Abad, Hiroko Nobuta, Jiaxi Li, Atsushi Kasai, William H. Yong, James A. Waschek

Research output: Contribution to journalArticlepeer-review

40 Scopus citations


Although the immune system may provide early protection against cancer, tumors may exploit the healing arm of the immune system to enhance their growth and metastasis. For example, myeloid derived suppressor cells (MDSCs) are thought to promote tumor growth by several mechanisms, including the suppression of T cell activity. It has been suggested that STAT3 activation in myeloid cells modulates multiple aspects of MDSC physiology, including their expansion and activity. Whereas most animal studies investigating tumor immunology have used tumor implants, we used transgenic mice (Smo*) that spontaneously develop medulloblastoma brain tumors to investigate the temporal accumulation of MDSCs within tumors and how myeloid STAT3 disruption affects MDSC and other immune cell types. We found distinct populations of MDSC in medulloblastoma tumors, with a high prevalence of CD11b+Ly6G+Ly6Clow/- cells, described previously by others as G-MDSCs. These were found early in tumor development, in premalignant lesions located on the surface of the cerebellum of 28-day-old mice. In fully developed tumors, pSTAT3 was found in the majority of these cells. Conditional STAT3 gene disruption in myeloid cells resulted in an enhanced proinflammatory phenotype of macrophages in Smo* mice. Moreover, a significant reduction in the abundance of G-MDSCs and Tregs was observed within tumors along with an increased presence of CD4+ and CD8+ cells. Despite these alterations in immune cells induced by myeloid STAT3 disruption, we found no effect on tumor incidence in Smo* mice with this deletion.

Original languageEnglish (US)
Pages (from-to)357-367
Number of pages11
JournalJournal of Leukocyte Biology
Issue number2
StatePublished - Feb 2014
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Cell Biology


  • Immunosuppression
  • Myeloid-derived suppressor cell
  • STAT3


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