Faculty Collaboration Database

Annexin-V promotes anti-tumor immunity and inhibits neuroblastoma growth in vivo. Cancer Immunol Immunother 2012 Nov;61(11):1917-27

Date

04/06/2012

Pubmed ID

22476407

DOI

10.1007/s00262-012-1250-4

Scopus ID

2-s2.0-84870984151 (requires institutional sign-in at Scopus site)   13 Citations

Abstract

The goal of the current study is to determine the effects of blocking phosphatidylserine (PS) on the growth of neuroblastoma in mice. PS, an anionic phospholipid restricted to the cytoplasmic surface of plasma membranes in most cells, is externalized to the surface of apoptotic cells. PS has been shown to induce immune tolerance to self-antigens. PS can also be found on the surface of live cells and in particular tumor cells. Annexin-V (AnV) is a protein that specifically binds and blocks PS. To determine the effects of blocking PS with AnV on tumor growth and immunogenicity, mice were inoculated with AGN2a, a poorly immunogenic murine neuroblastoma that expresses high level of PS on the cell surface. Survival and anti-tumor T cell response were determined. AGN2a were engineered to secrete AnV. Secreted protein effectively blocked tumor PS. 40 % of mice inoculated with AnV-expressing AGN2a cells survived free of tumor, whereas none of the mice inoculated with control cells survived (p = 0.0062). The benefits of AnV were lost when mice were depleted of T cells. The findings suggest that AnV could protect mice from tumor challenge through an immune mediated mechanism. Mice were then immunized with irradiated AnV-secreting or control cells, and challenged with wild-type AGN2a cells. AnV-secreting cell vaccine protected 80 % of mice from AGN2a challenge, while control cell vaccine prevented tumor growth in only 30 % of animals (p = 0.012). ELISPOT analysis demonstrated that AnV-secreting cell vaccine induced a greater frequency of interferon-gamma producing splenic T cells. T cells isolated from mice immunized with AnV-secreting but not control vaccine lysed AGN2a. In summary, AnV blocked PS, enhanced T cell mediated tumor immunity, and inhibited tumor growth.

Author List

Yan X, Doffek K, Yin C, Krein M, Phillips M, Sugg SL, Johnson B, Shilyansky J

Author

Bryon D. Johnson PhD Adjunct Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Annexin A5
Cell Survival
Immunotherapy
Interferon-gamma
Mice
Mice, Inbred Strains
Neuroblastoma
Phosphatidylserines
Self Tolerance
Spleen
T-Lymphocytes