Antibodies to IP-10 and MIG block IL-12-mediated T-cell infiltration and RENCA tumor regression (Meeting abstract).

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Antibodies to IP-10 and MIG block IL-12-mediated T-cell infiltration and RENCA tumor regression (Meeting abstract).

Proc Annu Meet Am Assoc Cancer Res; 38:A2394 1997. Unique Identifier : AIDSLINE ICDB/98639394
Tannenbaum C; Tubbs R; Finke J; Bukowsi R; Hamilton T; The Cleveland Clinic Foundation, Cleveland, OH 44195

Abstract: RENCA tumor tissue from IL-12 treated mice express mRNAs encoding the chemokine molecules IP-10 and MIG, are heavily infiltrated with CD8+ T cells, and express the cytolytic molecules perforin and granzyme B. Mice bearing RENCA tumors were treated with IL-12 in the presence or absence of intraperitoneally-administered antibodies against IP-10, MIG or both. Tumors grew progressively in RENCA tumor-bearing mice treated with control antibodies but was growth arrested and regressed in mice treated with IL-12 or IL-12 and normal rabbit IgG. Tumor growth was comparable to controls in animals treated with antibody raised against MIG or IP-10 alone. Tumors from mice treated with IL-12 in the presence of antibody to both IP-10 and MIG, however, did not regress, but rather demonstrated growth kinetics intermediate between those of IL-12-treated and untreated mice. Immunohistological analysis showed a strong CD8+ T cell infiltration into tumors from IL-12-treated mice and this was dramatically reduced in tumor tissue from mice treated with IL-12 in the presence of antibodies to both IP-10 and MIG. Perforin mRNA levels measured by RT-PCR in tumor tissue correlated directly with the level of T cell infiltration. These results demonstrate the importance of IP-10 and MIG expression for T cell recruitment in this tumor model and suggest that IL-12-mediated anti-tumor therapy requires chemokine expression as an intermediate step responsible for recruitment of activated T cells.

Keywords: Animal CD8-Positive T-Lymphocytes/*IMMUNOLOGY Cell Division/IMMUNOLOGY Chemokines/*IMMUNOLOGY Immunohistochemistry Interleukin-12/*ANTAGONISTS & INHIB *Lymphocytes, Tumor-Infiltrating Membrane Glycoproteins/GENETICS Mice Neoplasms, Experimental/*IMMUNOLOGY/PATHOLOGY RNA, Messenger/GENETICS/METABOLISM ABSTRACT
980228
M9820751

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