The B7x pathway in the tumor microenvironment One of the key issues in cancer immunotherapy is to identify the dominant escape mechanisms during different phases of tumor growth and to devise ways to overcome them. We have identified B7x as a poorly characterized member of the B7 family of T cell costimulation and coinhibition. Our clinical data have revealed that aberrant expression of B7x is observed in a variety of human cancers and is often associated with poor clinical outcome. The hypothesis of this project is that B7x is a critical immune evasion pathway within the tumor microenvironment and blockade of this pathway generates therapeutic tumor immunity. Guided by our published clinical research with cancer patients and our strong preliminary data with murine tumor models, this hypothesis will be tested by pursuing three specific aims: 1) Elucidation of the functional consequence of tumor-expressed B7x in disease progression;2) Determination of mechanistic contribution of host cell-expressed B7x to tumor progression;and 3) Generation of therapeutic tumor immunity by targeting the B7x pathway. We have generated a number of novel tools and have assembled a multi-disciplinary team with complementary skill sets, which provides us with unique opportunities to address challenges and realize goals. The outcomes of this research will provide novel insights into immune evasion mechanisms of the B7x pathway in the tumor microenvironment and provide the basis for future clinical design of a new immunotherapy.

Public Health Relevance

The proposed research is relevant to public health and NIH's mission, because our program will not only define a dominant escape mechanism within tumor microenvironment but also translate to new therapy opportunities for cancers.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
3R01CA175495-01A1S1
Application #
8843234
Study Section
Program Officer
Mccarthy, Susan A
Project Start
2014-07-01
Project End
2017-03-31
Budget Start
2014-07-01
Budget End
2015-03-31
Support Year
1
Fiscal Year
2014
Total Cost
$59,075
Indirect Cost
$23,701
Name
Albert Einstein College of Medicine
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
110521739
City
Bronx
State
NY
Country
United States
Zip Code
10461
Pawar, R D; Goilav, B; Xia, Y et al. (2015) B7x/B7-H4 modulates the adaptive immune response and ameliorates renal injury in antibody-mediated nephritis. Clin Exp Immunol 179:329-43
Jeon, Hyungjun; Vigdorovich, Vladimir; Garrett-Thomson, Sarah C et al. (2014) Structure and cancer immunotherapy of the B7 family member B7x. Cell Rep 9:1089-98