Cooperation between Constitutive and Inducible Chemokines Enables T-cell Engraftment and Immune Attack in Solid Tumors
By D. Dangaj, M. Bruand, Alizée J. Grimm, C. Ronet, D. Barras, Priyanka A. Duttagupta, E. Lanitis, Jaikumar Duraiswamy, J. Tanyi, F. Benencia and 17 more. Cancer Cell, 2019
719 citations recorded by the source corpus.
Summary 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 IFNγ-inducible, myeloid cell-secreted CXCL9. CCL5 and CXCL9 co-expression 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 lymphocytes (TILs) desertification whereas forced CCL5 expression prevented Cxcl9-expression and TILs loss and attenuated tumor growth in mice through IFNγ. The cooperation between tumor-derived CCL5 and IFNγ-inducible CXCR3 ligands secreted by myeloid cells is key for orchestrating T-cell infiltration in immunoreactive and immunoresponsive tumors.
Subfields: Immunology, Oncology
View Paper: https://www.semanticscholar.org/paper/4423d7d187dbfc00a88b918c3943b77a68ad64d7
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Citations in the corpus
- The Tumor Microenvironment: A Milieu Hindering and Obstructing Antitumor Immune Responses (2020, background): “CCL5 released by the tumor and CXCL9 released by APCs in response to IFN-γ seems crucial since CCL5hi CXCL9hi tumors are highly infiltrated with TILs and respond to checkpoint blockade inhibition (CPI) therapy (20).”
- Autophagy promotes immune evasion of pancreatic cancer by degrading MHC-I (2020, positive): “This is in line with a recent study showing that MHC-I-restricted antigen-recognition by CD8 + T cells can trigger DC activation, which further augments CD8 + T cell recruitment into the tumour 24 .”