The CXC chemokines IP-10 and Mig are necessary for IL-12-mediated regression of the mouse RENCA tumor.
The role of the non-ELR-containing CXC chemokines IP-10 and Mig in antitumor activity induced by systemic treatment with IL-12 was examined in mice bearing the murine renal adenocarcinoma RENCA. IL-12 treatment produces a potent antitumor effect that is associated with tumor infiltration by CD8+ T lymphocytes. The regression of tumor is associated with the elevated expression of the IFN-gamma-inducible chemokines IP-10 and Mig within the tumor tissue. IP-10 and Mig have been shown to function as chemoattractants for activated T lymphocytes. In animals treated with rabbit polyclonal Abs specific for IP-10 and for Mig, the IL-12-induced regression of RENCA tumors was partially abrogated. This effect was associated with a dramatic inhibition of T cell infiltration. Thus, it appears that IL-12-dependent, T cell-mediated antitumor activity requires the intermediate expression of IP-10 and Mig to recruit antitumor effector T cells to the tumor site.
Department of Immunology, Lerner Research Institute, Cleveland, OH 44195, USA.
C S
CS
Tannenbaum
R
R
Tubbs
D
D
Armstrong
J H
JH
Finke
R M
RM
Bukowski
T A
TA
Hamilton
D000595:Amino Acid Sequence; D000818:Animals; D000970:Antineoplastic Agents / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002292:Carcinoma, Renal Cell / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D002465:Cell Movement / Q000276:immunology; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D019743:Chemokines, CXC / Q000276:immunology / Q000502:physiology*; D007106:Immune Sera / Q000008:administration & dosage / Q000096:biosynthesis; D007274:Injections, Intraperitoneal; D018664:Interleukin-12 / Q000008:administration & dosage / Q000502:physiology*; D007680:Kidney Neoplasms / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009389:Neovascularization, Pathologic / Q000276:immunology; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D012333:RNA, Messenger / Q000096:biosynthesis
D000970:Antineoplastic Agents; C111954:CXC chemokine Mig; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D019743:Chemokines, CXC; D007106:Immune Sera; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D012333:RNA, Messenger; D054353:Perforin; D018664:Interleukin-12