Accession Number:

ADA595676

Title:

Reprogramming Antitumor Immune Responses with microRNAs

Descriptive Note:

Final rept. 30 Sep 2011-29 Sep 2013

Corporate Author:

WISTAR INST OF ANATOMY AND BIOLOGY PHILADELPHIA PA

Personal Author(s):

Report Date:

2013-10-01

Pagination or Media Count:

31.0

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.

Subject Categories:

  • Anatomy and Physiology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE