The Ovarian Cancer Chemokine Landscape Is Conducive to Homing of Vaccine-Primed and CD3/CD28-Costimulated T Cells Prepared for Adoptive Therapy.

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Serval ID
serval:BIB_87A4CCCAC4DE
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
The Ovarian Cancer Chemokine Landscape Is Conducive to Homing of Vaccine-Primed and CD3/CD28-Costimulated T Cells Prepared for Adoptive Therapy.
Journal
Clinical Cancer Research
Author(s)
Zsiros E., Duttagupta P., Dangaj D., Li H., Frank R., Garrabrant T., Hagemann I.S., Levine B.L., June C.H., Zhang L., Wang E., Marincola F.M., Bedognetti D., Powell D.J., Tanyi J., Feldman M.D., Kandalaft L.E., Coukos G.
ISSN
1078-0432 (Print)
ISSN-L
1078-0432
Publication state
Published
Issued date
2015
Peer-reviewed
Oui
Volume
21
Number
12
Pages
2840-2850
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't Publication Status: ppublish
Abstract
PURPOSE: Chemokines are implicated in T-cell trafficking. We mapped the chemokine landscape in advanced stage ovarian cancer and characterized the expression of cognate receptors in autologous dendritic cell (DC)-vaccine primed T cells in the context of cell-based immunotherapy.
EXPERIMENTAL DESIGN: The expression of all known human chemokines in patients with primary ovarian cancer was analyzed on two independent microarray datasets and validated on tissue microarray. Peripheral blood T cells from five HLA-A2 patients with recurrent ovarian cancer, who previously received autologous tumor DC vaccine, underwent CD3/CD28 costimulation and expansion ex vivo. Tumor-specific T cells were identified by HER2/neu pentamer staining and were evaluated for the expression and functionality of chemokine receptors important for homing to ovarian cancer.
RESULTS: The chemokine landscape of ovarian cancer is heterogeneous with high expression of known lymphocyte-recruiting chemokines (CCL2, CCL4, and CCL5) in tumors with intraepithelial T cells, whereas CXCL10, CXCL12, and CXCL16 are expressed quasi-universally, including in tumors lacking tumor-infiltrating T cells. DC-vaccine primed T cells were found to express the cognate receptors for the above chemokines. Ex vivo CD3/CD28 costimulation and expansion of vaccine-primed Tcells upregulated CXCR3 and CXCR4, and enhanced their migration toward universally expressed chemokines in ovarian cancer.
CONCLUSIONS: DC-primed tumor-specific T cells are armed with the appropriate receptors to migrate toward universal ovarian cancer chemokines, and these receptors are further upregulated by ex vivo CD3/CD28 costimulation, which render T cells more fit for migrating toward these chemokines. Clin Cancer Res; 21(12); 2840-50. ©2015 AACR.
Keywords
Antigens, CD28/metabolism, Antigens, CD3/metabolism, Biomarkers, Cancer Vaccines/immunology, Chemokines/genetics, Chemokines/metabolism, Chemotaxis, Leukocyte, Cluster Analysis, Dendritic Cells/immunology, Dendritic Cells/metabolism, Female, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Humans, Immunohistochemistry, Immunotherapy, Adoptive, Neoplasm Grading, Neoplasm Staging, Ovarian Neoplasms/diagnosis, Ovarian Neoplasms/genetics, T-Cell Antigen Receptor Specificity/immunology, T-Lymphocyte Subsets/immunology, T-Lymphocyte Subsets/metabolism
Pubmed
Web of science
Open Access
Yes
Create date
24/07/2015 18:13
Last modification date
20/08/2019 15:46
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