Principal Investigator/Program Director (Last, First, Middle):
Keller, Evan T./Zou, Weiping
DESCRIPTION: See instructions. State the application’s broad, long-term objectives and specific aims, making reference to the health relatedness of
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TITLE: Mechanistic interaction among Tregs, bone marrow cells, and prostate cancers
ABSTRACT: Bone marrow is the predetermined environment for tumor metastasis. Human prostate cancer
frequently metastasize to the bone marrow. It is thought that tumor bone marrow metastasis is determined
by the interaction between tumor and stroma cells including fibroblasts, osteoblasts and immune cells. As
tumor immunology and biology are traditionally viewed as distinct and unrelated disciplines, the mechanisms
whereby tumors metastasize to bone marrow have been largely defined in the context of tumor biology.
However, tumor growth and metastsis are controlled by functionally intertwined immunological and biological
networks in immune competent hosts. CD4+CD25+FOXP3+ regulatory T cells (Tregs) suppress tumor
associated antigen (TAA)- specific T cell immunity, and contribute to tumor growth and metastasis. High
prevalence of functional Tregs is found in human bone marrow, particularly in patients with prostate cancer.
Our current data support the notion that prostate cancer and bone marrow cells may alter Treg bone marrow
retention and function. We hypothesize that to ensure successful prostate bone marrow metastasis, Tregs
actively traffic into bone marrow, foster an immune privileged suppressive environment and contribute to
tumor bone metastasis whereas bone marrow and prostate cancer provide specific molecular signals for
Treg bone marrow retention, survival and expansion. Our specific aims are:
Aim 1: To test the hypothesis that Tregs and metastic prostate cancer cells reside in the similar and specific
“cellular and molecular code regions” in the bone marrow.
Aim 2: To test the hypothesis that bone marrow and prostate cancer provide specific molecular and cellular
signals for Treg bone marrow trafficking and retention.
Aim 3: To test the hypothesis that bone marrow and prostate cancer provide specific molecular and cellular
signals for Treg bone marrow survival and induction.
PERFORMANCE SITE(S) (organization, city, state)
The University of Michigan, Ann Arbor, Michigan
PHS 398 (Rev. 04/06)
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Principal Investigator/Program Director (Last, First, Middle):
Keller, Evan T./Zou, Weiping
KEY PERSONNEL. See instructions. Use continuation pages as needed to provide the required information in the format shown below.
Start with Principal Investigator(s). List all other key personnel in alphabetical order, last name first.
Name
eRA Commons User Name
Zou, Weiping
McCauley, Laurie
mccauley
OTHER SIGNIFICANT CONTRIBUTORS
Name
Organization
Role on Project
University of Michigan
Project Director
University of Michigan
Co-Investigator
Organization
Role on Project
X No
Yes
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Human Embryonic Stem Cells
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Cell Line
PHS 398 (Rev. 04/06)
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Form Page 2-continued
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the application. Do not use suffixes such as 4a, 4b.