Ovarian carcinoma-infiltrating regulatory T cells were more potent suppressors of CD8(+) T cell inflammation than their peripheral counterparts, a function dependent on TIM3 expression

Tumour Biol. 2016 Mar;37(3):3949-56. doi: 10.1007/s13277-015-4237-x. Epub 2015 Oct 19.

Abstract

Ovarian carcinoma is one of the most severe cancers in women, with a high relapse rate and limited secondary treatment options. To assist research in novel treatment technologies, including CD8(+) T cell-base immunotherapy, we examined the effect of tumor-infiltrating regulatory T cells (Tregs) in inhibiting CD8(+) T cell inflammation. We found that compared to their peripheral blood counterparts, tumor-infiltrating Tregs exhibited more potent inhibitory function, which was associated with higher interleukin 10 (IL-10) production in tumor-infiltrating Tregs. Blockade of T cell immunoglobulin mucin 3 (TIM3), a regulatory molecule overrepresented on tumor-infiltrating Tregs, had significantly reverted Treg-mediated suppression. Moreover, expression of TIM3 on tumor-infiltrating Tregs was directly correlated with tumor size. Together, our results demonstrated that ovarian tumor-infiltrating Treg cells were more immunosuppressive than their peripheral blood counterparts in a TIM3-dependent fashion.

Keywords: Ovarian cancer; Regulatory T cell; TIM3; Tumor-infiltrating lymphocyte.

MeSH terms

  • Adult
  • Aged
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Female
  • Hepatitis A Virus Cellular Receptor 2 / metabolism*
  • Humans
  • Immunosuppression Therapy
  • Interleukin-10 / biosynthesis
  • Lymphocyte Count
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Lymphocytes, Tumor-Infiltrating / metabolism
  • Middle Aged
  • Neoplasms, Glandular and Epithelial / blood
  • Neoplasms, Glandular and Epithelial / immunology*
  • Neoplasms, Glandular and Epithelial / pathology
  • Ovarian Neoplasms / blood
  • Ovarian Neoplasms / immunology*
  • Ovarian Neoplasms / pathology
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism
  • Tumor Burden

Substances

  • HAVCR2 protein, human
  • Hepatitis A Virus Cellular Receptor 2
  • IL10 protein, human
  • Interleukin-10