Title |
The role of The Xenopus Nonclassical MHC class I molecule XNC10 in Tumor Immunity
|
Institution |
UNIVERSITY OF ROCHESTER, ROCHESTER, NY
|
Principal Investigator |
BANACH, MAUREEN
|
NCI Program Director |
Banach
|
Cancer Activity |
Comp Min Biomed Prog
|
Division |
CRCHD
|
Funded Amount |
$43,120
|
Project Dates |
08/01/2015 - 06/30/2019
|
Fiscal Year |
2015
|
Project Type |
Grant
|
Research Topics w/ Percent Relevance |
Cancer Types w/ Percent Relevance |
Cancer (100.0%)
|
N/A
|
Research Type |
Cancer Progression & Metastasis
Systemic Therapies - Discovery and Development
|
Abstract |
DESCRIPTION (provided by applicant): The use of innate (i)T cells such as CD1d-restricted innate T cells for cancer immunotherapy requires a better understanding of their pro- and anti-tumoral properties. Using a comparative Xenopus tadpole cancer model we propose to investigate the role of Xenopus nonclassical MHC class Ib XNC10- restricted iT cells (functionally analogous to CD1d-restricted iNKT cells) in tumor immunity. Transplantation of Xenopus thymic lymphoid tumors (15/0) into naturally MHC class Ia-negative tadpoles has revealed that XNC10 molecule and XNC10-restricted iT cells contribute to tumor progression. Notably, silencing XNC10 gene expression in 15/0 tumor results in its acute immune rejection by syngeneic tadpoles with a significant infiltration of iT cells and macrophages. We hypothesize that XNC10-restricted iT cells, which are similar to mammalian CD1d-restricted iT cells; dictate lymphoid tumors rejection or progression by regulating macrophages. We will examine the effects of XNC10 loss-of-function at the tumor level and at the organism level (XNC10-iT cell-deficiency) as well as the effect of macrophage depletion and adoptive transfer of XNC10-iT cell on tumor immunity. Furthermore, to visualize how XNC10-restricted iT cells promote or prevent tumor grow by recruiting different immune effector cell types in tumor microenvironment we will apply real time intravital microscopy on a Xenopus semi-solid tumor collagen-embedded engraftment model. We anticipate that our findings will provide evolutionary evidence of the mechanism of class Ib-restricted iT cells in tumor immunity. " |