Cancer will affect 1 out of 2 men and 1 out of 3 women in their lifetime and is among one of the leading causes of death in the United State. Millions of dollars and hours are spent each year to find a cure, and yet cancer treatments continue to be less effective than desired. Treatments that involve radiation and toxic drugs often leave survivors with devastating side effects. This project will seek to provide an alternative treatment option for cancer patients that will have fewer short and long term side effects. The promising cancer treatment addressed by this project involves the utilization of the host immune system to combat existing cancers and possibly prevent new cancers. Currently it is known that the immune system has the potential to either inhibit or promote the growth of solid tumors by creating a tumor microenvironment that inhibit or promotes tumor growth. A greater understanding of these mechanisms is needed in order to successfully modulate the immune system to target cancer cells for destruction. To study how microRNA, a novel class of regulatory RNA, can be modulated within the immune system to promote better immune responses against tumors, the following aims will be addressed: 1) Determine the immunological role of miR-155 during de novo primary tumor formation and immunoediting, 2) Determine the immunological role of miR-155 during lung tumor metastasis.
These aims will address the hypothesis that MicroRNA- 155 plays a protective role during the formation of solid tumors by directing a competent immune response against de novo tumor formation and metastasizing tumor cells. Well- established genetic and carcinogenic models of tumor formation will be used to study the utility of microRNA modulation within the immune system in an effort to treat and prevent cancer. Upon its completion, this study will advance the field of cancer immunology. It will also improve the lives of cancer patients by increasing the ability of the medical community to modulate the immune system to fight cancers specifically with fewer harmful side effects.

Public Health Relevance

Cancer is one of the leading causes of death in the United States. Current therapies utilize a combination of radiation and toxic compounds that cause many side effects and long-term health challenges. This proposal seeks to understand the role of microRNA within the immune system in response to cancer formation. This effort will potentially lead to the use of microRNA within the immune system to combat cancer.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Individual Predoctoral NRSA for M.D./Ph.D. Fellowships (ADAMHA) (F30)
Project #
5F30CA189731-03
Application #
9110221
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Damico, Mark W
Project Start
2014-09-01
Project End
2018-08-31
Budget Start
2016-09-01
Budget End
2017-08-31
Support Year
3
Fiscal Year
2016
Total Cost
Indirect Cost
Name
University of Utah
Department
Pathology
Type
Schools of Medicine
DUNS #
009095365
City
Salt Lake City
State
UT
Country
United States
Zip Code
84112
Huffaker, Thomas B; Lee, Soh-Hyun; Tang, William W et al. (2017) Antitumor immunity is defective in T cell-specific microRNA-155-deficient mice and is rescued by immune checkpoint blockade. J Biol Chem 292:18530-18541