Reprogramming Antitumor Immune Responses with microRNAs

Abstract

During the tenure of this pilot project, we identified that miR-181a is universally up-regulated in ovarian cancer infiltrating lymphocytes. Unexpectedly, overexpression of miR-181a in anti-tumor (protective) T cells results in impaired effector functions in the tumor microenvironment, rather than in enhanced TCR recognition of tumor antigens. Genomic analysis of the genes silenced upon miR-181a up-regulation revealed a ~2-fold decrease in the expression of the enzyme Tryptophan 2,3-dioxygenase (TDO2), suggesting that impaired tryptophan metabolism may be the cause of defective responses by tumor-reactive T cells overexpressing miR-181a. No differences in immunological readouts were found between ovarian cancer-bearing hosts treated with cisplatin vs. oxiliplatin. Our results indicate that miR-181a impairs, rather than augmenting, T cell protection in ovarian cancer, and point to miR-181a as a novel target for down-regulating interventions.

Open PDF

Document Details

Document Type
Technical Report
Publication Date
Oct 01, 2013
Accession Number
ADA595676

Entities

People

  • Jose R Conejo-Garcia

Organizations

  • Wistar Institute

Tags

DTIC Thesaurus Topics

  • Adaptive Immunity
  • Biological Factors
  • Blood
  • Breast Cancer
  • Cancer
  • Cardiovascular System
  • Cell Physiological Processes
  • Cells
  • Epithelial Cells
  • Health Services
  • Lymphatic System
  • Lymphocytes
  • Peptides
  • Proteins

Fields of Study

  • Biology

Readers

  • Immunology
  • Oncology (Cancer Research).