Project title
子宮內膜癌與子宮頸腺癌免疫調控功能性差異研究
Internal ID
MOST107-2314-B002-154
Principal Investigator
Start Date
August 1, 2018
End Date
July 31, 2019
Investigators
Organizations
Partner Organizations
Functional Analysis of Differential Immune Regulations in Human Endometrial and Endocervial Adenocarcinoma = 子宮內膜癌與子宮頸腺癌免疫調控功能性差異研究
Description
Cancer immunotherapy is on-going in the clinical applications. Immunologic modulations with monoclonal antibodies have been utilized for treating a variety of cancer patients. In our previous unsupervised hierarchical clustering gene expression profiling studies, we find distinctive exemplifying inherent genetic and immunologic differences between human endometrial (EM) and endocervical (EC) adenocarcinomas, with selected immune regulating-subtypes. At present, little is known about the homeostasis and expression on tumor-infiltrating CD4+CD25+ FoxP3 regulatory T (TREG) cells in the human uterine cancer microenvironment. The effector functions of activated CD4+CD25+ FoxP3 TREG in cancer milieu are essential for elucidating the tumor immuno-pathogenesis. The present study will extend our previous findings and explore the kinetic regulations of tumor-infiltrating lymphocytes (TILs) with functional changes of FoxP3+ TREG cells in the human EM and EC adenocarcinomas. In the first year project, we will analyze the immuno-phenotypes and exploring the differential-expression of unsupervised hierarchical clustering gene profiles in fresh-isolated TILs by triple-color flow-cytometry. Our focus is concentrated on the expression of activation markers on CD3+CD25+ FoxP3+ TILs. In the second year project, we will investigate the homeostasis and functional lineage-expressions in CD4+ T cells, CD8+T cells to stratify the functional roles in correlated clustering gene profiles and cytokine receptors on immuno-sorted subsets of TREG. The kinetic activity with concordant expression of basic activation analyses of CD4+ T cells, CD8+ T cells, and NK-T cells will be illustrated between EM & EC cancer groups. In the third year project, we will explore the possible regulatory roles of cytokines on the kinetic activity with concordant expressions of certain TCR receptors on the TREG cells between. EM & EC cancer groups. The functional change of TREG cells will be evaluated and linked to the accumulated immuno-phenotypic functional assays in subjects with human EM and EC adenocarcinomas cancers. Our studies will shed new lights on the Immunologic modulations of cancer therapy in human corpus EM & EC cancers.