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Chemokine nitration prevents intratumoral infiltration of antigen-specific T cells
- Source :
- The Journal of Experimental Medicine, The Journal of experimental medicine 208 (2011): 1949–1962., info:cnr-pdr/source/autori:Molon B, Ugel S, Del Pozzo F, Soldani C, Zilio S, Avella D, De Palma A, Mauri P, Monegal A, Rescigno M, Savino B, Colombo P, Jonjic N, Pecanic S, Lazzarato L, Fruttero R, Gasco A, Bronte V, Viola A./titolo:Chemokine nitration prevents intratumoral infiltration of antigen-specific T cells./doi:/rivista:The Journal of experimental medicine/anno:2011/pagina_da:1949/pagina_a:1962/intervallo_pagine:1949–1962/volume:208
- Publication Year :
- 2011
-
Abstract
- Blocking CCL2 nitration in tumors promoted CD8+ influx and reduced tumor growth and prolonged survival in mice when combined with adoptive cell therapy.<br />Tumor-promoted constraints negatively affect cytotoxic T lymphocyte (CTL) trafficking to the tumor core and, as a result, inhibit tumor killing. The production of reactive nitrogen species (RNS) within the tumor microenvironment has been reported in mouse and human cancers. We describe a novel RNS-dependent posttranslational modification of chemokines that has a profound impact on leukocyte recruitment to mouse and human tumors. Intratumoral RNS production induces CCL2 chemokine nitration and hinders T cell infiltration, resulting in the trapping of tumor-specific T cells in the stroma that surrounds cancer cells. Preconditioning of the tumor microenvironment with novel drugs that inhibit CCL2 modification facilitates CTL invasion of the tumor, suggesting that these drugs may be effective in cancer immunotherapy. Our results unveil an unexpected mechanism of tumor evasion and introduce new avenues for cancer immunotherapy.
- Subjects :
- Chemokine
Adoptive cell transfer
Cytotoxic
medicine.medical_treatment
T-Lymphocytes
Inbred C57BL
COLORECTAL-CANCER
Mice
Cancer immunotherapy
Cell Movement
T-Lymphocyte Subsets
T lymphocyte
Tumor Microenvironment
Cytotoxic T cell
Immunology and Allergy
Adoptive Transfer
Animals
Cell Line, Tumor
Chemokine CCL2
Chemokine CXCL12
Colorectal Neoplasms
Humans
Immunotherapy
Mice, Inbred BALB C
Mice, Inbred C57BL
Reactive Nitrogen Species
T-Lymphocytes, Cytotoxic
Protein Processing, Post-Translational
Immunology
IN-VIVO
Inbred BALB C
Tumor
biology
IMMUNE-RESPONSES
Nitration
cancer
myeloid-derived suppressor cells
immmune evasion
chemokine
PROSTATE-CANCER
CANCER-IMMUNOTHERAPY
TUMOR
TYROSINE NITRATION
MYELOID SUPPRESSOR-CELLS
MONOCYTE CHEMOTACTIC PROTEIN-1
CCL2
Article
Cell Line
medicine
Protein Processing
Tumor microenvironment
Post-Translational
chemokine nitration
intratumoral infiltration
antigen-specific T cells
CTL
Cancer cell
biology.protein
Cancer research
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- The Journal of Experimental Medicine, The Journal of experimental medicine 208 (2011): 1949–1962., info:cnr-pdr/source/autori:Molon B, Ugel S, Del Pozzo F, Soldani C, Zilio S, Avella D, De Palma A, Mauri P, Monegal A, Rescigno M, Savino B, Colombo P, Jonjic N, Pecanic S, Lazzarato L, Fruttero R, Gasco A, Bronte V, Viola A./titolo:Chemokine nitration prevents intratumoral infiltration of antigen-specific T cells./doi:/rivista:The Journal of experimental medicine/anno:2011/pagina_da:1949/pagina_a:1962/intervallo_pagine:1949–1962/volume:208
- Accession number :
- edsair.doi.dedup.....de16df1b84e9d8641e90dfc0dd9a99e5