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

Publication ,  Journal Article
Dangaj, D; Bruand, M; Grimm, AJ; Ronet, C; Barras, D; Duttagupta, PA; Lanitis, E; Duraiswamy, J; Tanyi, JL; Benencia, F; Conejo-Garcia, J ...
Published in: Cancer Cell
June 10, 2019

We investigated the role of chemokines in regulating T cell accumulation in solid tumors. CCL5 and CXCL9 overexpression was associated with CD8+ 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.

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Published In

Cancer Cell

DOI

EISSN

1878-3686

Publication Date

June 10, 2019

Volume

35

Issue

6

Start / End Page

885 / 900.e10

Location

United States

Related Subject Headings

  • Signal Transduction
  • Receptors, CXCR3
  • Paracrine Communication
  • Ovarian Neoplasms
  • Oncology & Carcinogenesis
  • Mice, Inbred C57BL
  • Macrophages
  • Lymphocytes, Tumor-Infiltrating
  • Lymphocyte Activation
  • Interferon-gamma
 

Citation

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Dangaj, D., Bruand, M., Grimm, A. J., Ronet, C., Barras, D., Duttagupta, P. A., … Coukos, G. (2019). Cooperation between Constitutive and Inducible Chemokines Enables T Cell Engraftment and Immune Attack in Solid Tumors. Cancer Cell, 35(6), 885-900.e10. https://doi.org/10.1016/j.ccell.2019.05.004
Dangaj, Denarda, Marine Bruand, Alizée J. Grimm, Catherine Ronet, David Barras, Priyanka A. Duttagupta, Evripidis Lanitis, et al. “Cooperation between Constitutive and Inducible Chemokines Enables T Cell Engraftment and Immune Attack in Solid Tumors.Cancer Cell 35, no. 6 (June 10, 2019): 885-900.e10. https://doi.org/10.1016/j.ccell.2019.05.004.
Dangaj D, Bruand M, Grimm AJ, Ronet C, Barras D, Duttagupta PA, et al. Cooperation between Constitutive and Inducible Chemokines Enables T Cell Engraftment and Immune Attack in Solid Tumors. Cancer Cell. 2019 Jun 10;35(6):885-900.e10.
Dangaj, Denarda, et al. “Cooperation between Constitutive and Inducible Chemokines Enables T Cell Engraftment and Immune Attack in Solid Tumors.Cancer Cell, vol. 35, no. 6, June 2019, pp. 885-900.e10. Pubmed, doi:10.1016/j.ccell.2019.05.004.
Dangaj D, Bruand M, Grimm AJ, Ronet C, Barras D, Duttagupta PA, Lanitis E, Duraiswamy J, Tanyi JL, Benencia F, Conejo-Garcia J, Ramay HR, Montone KT, Powell DJ, Gimotty PA, Facciabene A, Jackson DG, Weber JS, Rodig SJ, Hodi SF, Kandalaft LE, Irving M, Zhang L, Foukas P, Rusakiewicz S, Delorenzi M, Coukos G. Cooperation between Constitutive and Inducible Chemokines Enables T Cell Engraftment and Immune Attack in Solid Tumors. Cancer Cell. 2019 Jun 10;35(6):885-900.e10.

Published In

Cancer Cell

DOI

EISSN

1878-3686

Publication Date

June 10, 2019

Volume

35

Issue

6

Start / End Page

885 / 900.e10

Location

United States

Related Subject Headings

  • Signal Transduction
  • Receptors, CXCR3
  • Paracrine Communication
  • Ovarian Neoplasms
  • Oncology & Carcinogenesis
  • Mice, Inbred C57BL
  • Macrophages
  • Lymphocytes, Tumor-Infiltrating
  • Lymphocyte Activation
  • Interferon-gamma