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) : Conejo-Garcia, Jose R


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a595676.pdf


Report Date : Oct 2013


Pagination or Media Count : 31


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.


Descriptors :   *CANCER , *IMMUNOLOGY , CHEMOTHERAPY , ENZYMES , GENES , GENOME , OVARIES , RESPONSE(BIOLOGY) , T LYMPHOCYTES


Subject Categories : Anatomy and Physiology
      Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE