Mac-1 (CD11b/CD18) is crucial for effective Fc receptor-mediated immunity to melanoma.
Antibody-reliant destruction of tumor cells by immune effector cells is mediated by antibody-dependent cellular cytotoxicity, in which Fc receptor (FcR) engagement is crucial. This study documents an important role for the beta(2) integrin Mac-1 (CD11b/CD18) in FcR-mediated protection against melanoma. CD11b-deficient mice, those that lack Mac-1, were less protected by melanoma-specific monoclonal antibody TA99 than wild-type (WT) mice. Significantly more lung metastases and higher tumor loads were observed in Mac-1(-/-) mice. Histologic analyses revealed no differences in neutrophil infiltration of lung tumors between Mac-1(-/-) and WT mice. Importantly, Mac-1(-/-) phagocytes retained the capacity to bind tumor cells, implying that Mac-1 is essential during actual FcR-mediated cytotoxicity. In summary, this study documents Mac-1 to be required for FcR-mediated antimelanoma immunity in vivo and, furthermore, supports a role for neutrophils in melanoma rejection.
van Spriel
Annemiek B
AB
Immunotherapy Laboratory, Department of Immunology, University Medical Center Utrecht, The Netherlands.
van Ojik
Heidi H
HH
Bakker
Annie
A
Jansen
Marco J H
MJ
van de Winkel
Jan G J
JG
D000818:Animals; D000912:Antibodies, Neoplasm; D000917:Antibody Formation; D039481:CD11b Antigen / Q000235:genetics / Q000276:immunology; D002634:Chemotaxis, Leukocyte; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D008175:Lung Neoplasms / Q000556:secondary; D016177:Macrophage-1 Antigen / Q000235:genetics / Q000276:immunology*; D008545:Melanoma / Q000276:immunology* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009504:Neutrophils / Q000166:cytology; D011961:Receptors, Fc / Q000276:immunology*
D000912:Antibodies, Neoplasm; D039481:CD11b Antigen; D016177:Macrophage-1 Antigen; D011961:Receptors, Fc; D016179:Granulocyte Colony-Stimulating Factor