Cooperation between Constitutive and Inducible Chemokines Enables T Cell Engraftment and Immune Attack in Solid Tumors.

Details

Serval ID
serval:BIB_95C8776874F3
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Cooperation between Constitutive and Inducible Chemokines Enables T Cell Engraftment and Immune Attack in Solid Tumors.
Journal
Cancer cell
Author(s)
Dangaj D., Bruand M., Grimm A.J., Ronet C., Barras D., Duttagupta P.A., Lanitis E., Duraiswamy J., Tanyi J.L., Benencia F., Conejo-Garcia J., Ramay H.R., Montone K.T., Powell D.J., Gimotty P.A., Facciabene A., Jackson D.G., Weber J.S., Rodig S.J., Hodi S.F., Kandalaft L.E., Irving M., Zhang L., Foukas P., Rusakiewicz S., Delorenzi M., Coukos G.
ISSN
1878-3686 (Electronic)
ISSN-L
1535-6108
Publication state
Published
Issued date
10/06/2019
Peer-reviewed
Oui
Volume
35
Number
6
Pages
885-900.e10
Language
english
Notes
Publication types: Journal Article ; Research Support, American Recovery and Reinvestment Act ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
We investigated the role of chemokines in regulating T cell accumulation in solid tumors. CCL5 and CXCL9 overexpression was associated with CD8 <sup>+</sup> T cell infiltration in solid tumors. T cell infiltration required tumor cell-derived CCL5 and was amplified by IFN-γ-inducible, myeloid cell-secreted CXCL9. CCL5 and CXCL9 coexpression revealed immunoreactive tumors with prolonged survival and response to checkpoint blockade. Loss of CCL5 expression in human tumors was associated with epigenetic silencing through DNA methylation. Reduction of CCL5 expression caused tumor-infiltrating lymphocyte (TIL) desertification, whereas forced CCL5 expression prevented Cxcl9 expression and TILs loss, and attenuated tumor growth in mice through IFN-γ. The cooperation between tumor-derived CCL5 and IFN-γ-inducible CXCR3 ligands secreted by myeloid cells is key for orchestrating T cell infiltration in immunoreactive and immunoresponsive tumors.
Keywords
Animals, Antineoplastic Agents, Immunological/pharmacology, CD8-Positive T-Lymphocytes/drug effects, CD8-Positive T-Lymphocytes/immunology, CD8-Positive T-Lymphocytes/metabolism, Cell Line, Tumor, Chemokine CCL5/genetics, Chemokine CCL5/immunology, Chemokine CCL5/metabolism, Chemokine CXCL9/genetics, Chemokine CXCL9/immunology, Chemokine CXCL9/metabolism, Chemotaxis, Leukocyte/drug effects, Coculture Techniques, Cytokines/genetics, Cytokines/immunology, Cytokines/metabolism, DNA Methylation, Dendritic Cells/drug effects, Dendritic Cells/immunology, Dendritic Cells/metabolism, Epigenesis, Genetic, Female, Gene Expression Regulation, Neoplastic, Humans, Immunotherapy/methods, Interferon-gamma/genetics, Interferon-gamma/immunology, Interferon-gamma/metabolism, Lymphocyte Activation/drug effects, Lymphocytes, Tumor-Infiltrating/drug effects, Lymphocytes, Tumor-Infiltrating/immunology, Lymphocytes, Tumor-Infiltrating/metabolism, Macrophages/drug effects, Macrophages/immunology, Macrophages/metabolism, Mice, Inbred C57BL, Ovarian Neoplasms/immunology, Ovarian Neoplasms/metabolism, Ovarian Neoplasms/pathology, Ovarian Neoplasms/therapy, Paracrine Communication, Receptors, CXCR3/genetics, Receptors, CXCR3/immunology, Receptors, CXCR3/metabolism, Signal Transduction, CCL5, CXCL10, CXCL9, IFN-γ, T cell trafficking in the tumor, TILs (tumor-infiltrating lymphocytes), checkpoint blockade, epigenetic silencing, immunoreactive tumors, inducible and constitutive chemokines
Pubmed
Web of science
Create date
24/06/2019 8:13
Last modification date
05/04/2020 6:20
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