Adoptive transfer of tumor-specific Tc17 effector T cells controls the growth of B16 melanoma in mice.
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-gamma 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-gamma 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.
Trudeau Institute, Saranac Lake, NY 12983, USA.
Maria de la Luz
Mde L
Garcia-Hernandez
Hiromasa
H
Hamada
Joyce B
JB
Reome
Sara K
SK
Misra
Michael P
MP
Tighe
Richard W
RW
Dutton
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000637:transplantation*; D045744:Cell Line, Tumor; D003601:Cytotoxicity Tests, Immunologic; D004195:Disease Models, Animal; D005260:Female; D016219:Immunotherapy, Adoptive / Q000379:methods*; D020381:Interleukin-17 / Q000096:biosynthesis* / Q000502:physiology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000473:pathology; D008546:Melanoma, Experimental / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009367:Neoplasm Staging; D010047:Ovalbumin / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000473:pathology / Q000637:transplantation
D020381:Interleukin-17; D010047:Ovalbumin