The activation NKG2D receptor has been shown to play an important role in the control of experimental tumor growth and metastases expressing ligands for NKG2D; however, a function for this recognition pathway in host protection from de novo tumorigenesis has never been demonstrated. We show that neutralization of NK62D enhances the sensitivity of wild-type (WT) C57BL/6 and BALB/c mice to methylcholanthrene (MCA)-induced fibrosarcoma. The importance of the NK62D pathway was additionally illustrated in mice deficient for either IFN-gamma or tumor necrosis factor-related apoptosis-inducing ligand, whereas mice depleted of natural killer cells, T cells, or deficient for perforin did not display any detectable NKG2D phenotype. Furthermore, IL-12 therapy preventing MCA-induced sarcoma formation was also largely dependent on the NK62D pathway. Although NK62D ligand expression was variable or absent on sarcomas emerging in WT mice, sarcomas derived from perforin-deficient mice were Rae-1(+) and immunogenic when transferred into WT syngeneic mice. These findings suggest an important early role for the NKG2D in controlling and shaping tumor formation.
机构:
Fred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave North, Seattle, WA 98109 USA
Tech Univ Munich, Inst Microbiol, Trogerstr 32, D-81675 Munich, GermanyFred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave North, Seattle, WA 98109 USA
Bauer, Stefan
;
Groh, Veronika
论文数: 0引用数: 0
h-index: 0
机构:
Fred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave North, Seattle, WA 98109 USAFred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave North, Seattle, WA 98109 USA
Groh, Veronika
;
Wu, Jun
论文数: 0引用数: 0
h-index: 0
机构:
DNAX Res Inst Mol & Cellular Biol Inc, 901 Calif Ave, Palo Alto, CA 94304 USAFred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave North, Seattle, WA 98109 USA
Wu, Jun
;
Steinle, Alexander
论文数: 0引用数: 0
h-index: 0
机构:
Fred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave North, Seattle, WA 98109 USAFred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave North, Seattle, WA 98109 USA
Steinle, Alexander
;
Phillips, Joseph H.
论文数: 0引用数: 0
h-index: 0
机构:
DNAX Res Inst Mol & Cellular Biol Inc, 901 Calif Ave, Palo Alto, CA 94304 USAFred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave North, Seattle, WA 98109 USA
Phillips, Joseph H.
;
Lanier, Lewis L.
论文数: 0引用数: 0
h-index: 0
机构:
DNAX Res Inst Mol & Cellular Biol Inc, 901 Calif Ave, Palo Alto, CA 94304 USAFred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave North, Seattle, WA 98109 USA
Lanier, Lewis L.
;
Spies, Thomas
论文数: 0引用数: 0
h-index: 0
机构:
Fred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave North, Seattle, WA 98109 USAFred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave North, Seattle, WA 98109 USA
机构:Guys Kings St Thomas Med Sch, Peter Gorer Dept Immunobiol, London SE1 9RT, England
Girardi, M
;
Oppenheim, DE
论文数: 0引用数: 0
h-index: 0
机构:Guys Kings St Thomas Med Sch, Peter Gorer Dept Immunobiol, London SE1 9RT, England
Oppenheim, DE
;
Steele, CR
论文数: 0引用数: 0
h-index: 0
机构:Guys Kings St Thomas Med Sch, Peter Gorer Dept Immunobiol, London SE1 9RT, England
Steele, CR
;
Lewis, JM
论文数: 0引用数: 0
h-index: 0
机构:Guys Kings St Thomas Med Sch, Peter Gorer Dept Immunobiol, London SE1 9RT, England
Lewis, JM
;
Glusac, E
论文数: 0引用数: 0
h-index: 0
机构:Guys Kings St Thomas Med Sch, Peter Gorer Dept Immunobiol, London SE1 9RT, England
Glusac, E
;
Filler, R
论文数: 0引用数: 0
h-index: 0
机构:Guys Kings St Thomas Med Sch, Peter Gorer Dept Immunobiol, London SE1 9RT, England
Filler, R
;
Hobby, P
论文数: 0引用数: 0
h-index: 0
机构:Guys Kings St Thomas Med Sch, Peter Gorer Dept Immunobiol, London SE1 9RT, England
Hobby, P
;
Sutton, B
论文数: 0引用数: 0
h-index: 0
机构:Guys Kings St Thomas Med Sch, Peter Gorer Dept Immunobiol, London SE1 9RT, England
Sutton, B
;
Tigelaar, RE
论文数: 0引用数: 0
h-index: 0
机构:Guys Kings St Thomas Med Sch, Peter Gorer Dept Immunobiol, London SE1 9RT, England
Tigelaar, RE
;
Hayday, AC
论文数: 0引用数: 0
h-index: 0
机构:
Guys Kings St Thomas Med Sch, Peter Gorer Dept Immunobiol, London SE1 9RT, EnglandGuys Kings St Thomas Med Sch, Peter Gorer Dept Immunobiol, London SE1 9RT, England
机构:
Fred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave North, Seattle, WA 98109 USA
Tech Univ Munich, Inst Microbiol, Trogerstr 32, D-81675 Munich, GermanyFred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave North, Seattle, WA 98109 USA
Bauer, Stefan
;
Groh, Veronika
论文数: 0引用数: 0
h-index: 0
机构:
Fred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave North, Seattle, WA 98109 USAFred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave North, Seattle, WA 98109 USA
Groh, Veronika
;
Wu, Jun
论文数: 0引用数: 0
h-index: 0
机构:
DNAX Res Inst Mol & Cellular Biol Inc, 901 Calif Ave, Palo Alto, CA 94304 USAFred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave North, Seattle, WA 98109 USA
Wu, Jun
;
Steinle, Alexander
论文数: 0引用数: 0
h-index: 0
机构:
Fred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave North, Seattle, WA 98109 USAFred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave North, Seattle, WA 98109 USA
Steinle, Alexander
;
Phillips, Joseph H.
论文数: 0引用数: 0
h-index: 0
机构:
DNAX Res Inst Mol & Cellular Biol Inc, 901 Calif Ave, Palo Alto, CA 94304 USAFred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave North, Seattle, WA 98109 USA
Phillips, Joseph H.
;
Lanier, Lewis L.
论文数: 0引用数: 0
h-index: 0
机构:
DNAX Res Inst Mol & Cellular Biol Inc, 901 Calif Ave, Palo Alto, CA 94304 USAFred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave North, Seattle, WA 98109 USA
Lanier, Lewis L.
;
Spies, Thomas
论文数: 0引用数: 0
h-index: 0
机构:
Fred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave North, Seattle, WA 98109 USAFred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave North, Seattle, WA 98109 USA
机构:Guys Kings St Thomas Med Sch, Peter Gorer Dept Immunobiol, London SE1 9RT, England
Girardi, M
;
Oppenheim, DE
论文数: 0引用数: 0
h-index: 0
机构:Guys Kings St Thomas Med Sch, Peter Gorer Dept Immunobiol, London SE1 9RT, England
Oppenheim, DE
;
Steele, CR
论文数: 0引用数: 0
h-index: 0
机构:Guys Kings St Thomas Med Sch, Peter Gorer Dept Immunobiol, London SE1 9RT, England
Steele, CR
;
Lewis, JM
论文数: 0引用数: 0
h-index: 0
机构:Guys Kings St Thomas Med Sch, Peter Gorer Dept Immunobiol, London SE1 9RT, England
Lewis, JM
;
Glusac, E
论文数: 0引用数: 0
h-index: 0
机构:Guys Kings St Thomas Med Sch, Peter Gorer Dept Immunobiol, London SE1 9RT, England
Glusac, E
;
Filler, R
论文数: 0引用数: 0
h-index: 0
机构:Guys Kings St Thomas Med Sch, Peter Gorer Dept Immunobiol, London SE1 9RT, England
Filler, R
;
Hobby, P
论文数: 0引用数: 0
h-index: 0
机构:Guys Kings St Thomas Med Sch, Peter Gorer Dept Immunobiol, London SE1 9RT, England
Hobby, P
;
Sutton, B
论文数: 0引用数: 0
h-index: 0
机构:Guys Kings St Thomas Med Sch, Peter Gorer Dept Immunobiol, London SE1 9RT, England
Sutton, B
;
Tigelaar, RE
论文数: 0引用数: 0
h-index: 0
机构:Guys Kings St Thomas Med Sch, Peter Gorer Dept Immunobiol, London SE1 9RT, England
Tigelaar, RE
;
Hayday, AC
论文数: 0引用数: 0
h-index: 0
机构:
Guys Kings St Thomas Med Sch, Peter Gorer Dept Immunobiol, London SE1 9RT, EnglandGuys Kings St Thomas Med Sch, Peter Gorer Dept Immunobiol, London SE1 9RT, England