Adoptive Transfer of Tumor-Specific Tc17 Effector T Cells Controls the Growth of B16 Melanoma in Mice
Open Access
- 15 April 2010
- journal article
- research article
- Published by The American Association of Immunologists
- Vol. 184 (8), 4215-4227
- https://doi.org/10.4049/jimmunol.0902995
Abstract
In vitro generated OVA-specific IL-17–producing CD8 T effector cells (Tc17) from OT-1 mice, adoptively transferred into B16-OVA tumor-bearing mice, controlled tumor growth in early and late stage melanoma. IL-17, TNF, and IFN-γ from the Tc17 effectors all played a role in an enhanced recruitment of T cells, neutrophils, and macrophages to the tumor. In addition, Tc17 cells and recently recruited, activated neutrophils produced further chemokines, including CCL3, CCL4, CCL5, CXCL9, and CXCL10, responsible for the attraction of type 1 lymphocytes (Th1 and Tc1) and additional neutrophils. Neutrophils were rapidly attracted to the tumor site by an IL-17 dependent mechanism, but at later stages the induction of the chemokine CXCL2 by Tc17-derived TNF and IFN-γ contributed to sustain neutrophil recruitment. Approximately 10–50 times as many Tc17 effectors were required compared with Tc1 effectors to exert the same level of control over tumor growth. The recruitment of neutrophils was more prominent when Tc17 rather than Tc1 were used to control tumor and depletion of neutrophils resulted in a diminished capacity to control tumor growth.Keywords
This publication has 50 references indexed in Scilit:
- Tc17, a Unique Subset of CD8 T Cells That Can Protect against Lethal Influenza ChallengePublished by The American Association of Immunologists ,2009
- Tumor-specific Th17-polarized cells eradicate large established melanomaBlood, 2008
- Phenotypic Analysis of Prostate-Infiltrating Lymphocytes Reveals TH17 and Treg SkewingClinical Cancer Research, 2008
- Identification of an IL-17–producing NK1.1neg iNKT cell population involved in airway neutrophiliaThe Journal of Experimental Medicine, 2007
- Cancer Regression in Patients After Transfer of Genetically Engineered LymphocytesScience, 2006
- Effector Cell-Derived Lymphotoxin α and Fas Ligand, but not Perforin, Promote Tc1 and Tc2 Effector Cell-Mediated Tumor Therapy in Established Pulmonary MetastasesCancer Research, 2004
- IL-17 in synovial fluids from patients with rheumatoid arthritis is a potent stimulator of osteoclastogenesisJCI Insight, 1999
- Interleukin-17-induced Gene Expression in Articular Chondrocytes Is Associated with Activation of Mitogen-activated Protein Kinases and NF-κBPublished by Elsevier BV ,1998
- Cytotoxicity mediated by T cells and natural killer cells is greatly impaired in perforin-deficient miceNature, 1994
- A Progress Report on the Treatment of 157 Patients with Advanced Cancer Using Lymphokine-Activated Killer Cells and Interleukin-2 or High-Dose Interleukin-2 AloneNew England Journal of Medicine, 1987