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Blood, 1 January 2003, Vol. 101, No. 1, pp. 253-258
IMMUNOBIOLOGY
Mac-1 (CD11b/CD18) is crucial for effective Fc
receptor-mediated immunity to melanoma
Annemiek B. van Spriel,
Heidi H. van Ojik,
Annie Bakker,
Marco J. H. Jansen, and
Jan G. J. van de
Winkel
From the Immunotherapy Laboratory, Department of
Immunology, Department of Internal Medicine and Oncology, Medarex
Europe, and Genmab, University Medical Center Utrecht, The
Netherlands.
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  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.
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