Adoptive transfer of cytotoxic T lymphocytes (CTL) represents an exciting mode of immunotherapy of human cancer. However, it is well known that large established tumors are very resistant to this type of immunotherapy. This proposal is based on our recent observation that targeting activation induced cytidine deaminase (AID) can render large established tumors to be rejected by CTL transfer. Further analysis of AID-eliminated, CTL-rejectable tumor cells revealed CD200 expression on tumor cells is responsible for tumor rejection. This proposal aims to explore the roles of CD200- CD200 receptor (R) pathway in T cell therapy of cancer. Our overall hypothesis is that enhancing CD200-CD200R interaction modulates tumor rejection by CTL through inhibition of the functions of tumor associated myeloid cells.
The specific aims of this proposal are: (1) to investigate the roles of CD200-CD200R interaction in CTL therapy of multiple lineages of experimental tumors;(2) to determine mechanisms by which CD200 expression on tumor cells impact T cell therapy of cancer and (3) to test if stimulating CD200R using agonistic antibody or CD200-Fc fusion protein can enhance CTL therapy of cancer. If successful, our proposed experiments will not only reveal new insights in CTL-mediated tumor rejection mechanisms, but also provide a basis for a novel therapy of human cancer.

Public Health Relevance

In this proposal we propose to study the roles of CD200-CD200 receptor interaction in cytotoxic T lymphocyte (CTL) therapy of cancer. Our proposed experiments will not only reveal new insights in CTL-mediated tumor rejection mechanisms, but also provide a basis for a novel therapy of human cancer.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA138427-03
Application #
8009851
Study Section
Cancer Immunopathology and Immunotherapy Study Section (CII)
Program Officer
Mccarthy, Susan A
Project Start
2009-02-06
Project End
2012-12-31
Budget Start
2011-01-01
Budget End
2011-12-31
Support Year
3
Fiscal Year
2011
Total Cost
$241,530
Indirect Cost
Name
Ohio State University
Department
Pathology
Type
Schools of Medicine
DUNS #
832127323
City
Columbus
State
OH
Country
United States
Zip Code
43210
Liu, Jin-Qing; Talebian, Fatemeh; Wu, Lisha et al. (2016) A Critical Role for CD200R Signaling in Limiting the Growth and Metastasis of CD200+ Melanoma. J Immunol 197:1489-97
Wang, Lixin; Liu, Jin-Qing; Talebian, Fatemeh et al. (2015) IL-10 enhances CTL-mediated tumor rejection by inhibiting highly suppressive CD4(+) T cells and promoting CTL persistence in a murine model of plasmacytoma. Oncoimmunology 4:e1014232
Li, Ming-Song; Liu, Zhenzhen; Liu, Jin-Qing et al. (2015) The Yin and Yang aspects of IL-27 in induction of cancer-specific T-cell responses and immunotherapy. Immunotherapy 7:191-200
Liu, Zhenzhen; Liu, Jin-Qing; Shi, Yun et al. (2015) Epstein-Barr virus-induced gene 3-deficiency leads to impaired antitumor T-cell responses and accelerated tumor growth. Oncoimmunology 4:e989137
Liao, Kang-Ling; Bai, Xue-Feng; Friedman, Avner (2014) Mathematical modeling of Interleukin-35 promoting tumor growth and angiogenesis. PLoS One 9:e110126
Liao, Kang-Ling; Bai, Xue-Feng; Friedman, Avner (2014) Mathematical modeling of interleukin-27 induction of anti-tumor T cells response. PLoS One 9:e91844
Chu, Jianhong; He, Shun; Deng, Youcai et al. (2014) Genetic modification of T cells redirected toward CS1 enhances eradication of myeloma cells. Clin Cancer Res 20:3989-4000
Liu, Zhenzhen; Liu, Jin-Qing; Talebian, Fatemeh et al. (2013) IL-27 enhances the survival of tumor antigen-specific CD8+ T cells and programs them into IL-10-producing, memory precursor-like effector cells. Eur J Immunol 43:468-79
Liu, Zhenzhen; Yu, Jianhua; Carson 3rd, William E et al. (2013) The role of IL-27 in the induction of anti-tumor cytotoxic T lymphocyte response. Am J Transl Res 5:470-80
Wang, Li-Xin; Mei, Zhen-Yang; Zhou, Ji-Hao et al. (2013) Low dose decitabine treatment induces CD80 expression in cancer cells and stimulates tumor specific cytotoxic T lymphocyte responses. PLoS One 8:e62924

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