Intralesional treatment of established murine primary renal tumor with interleukin-4: localized effect on primary tumor with no impact on metastases.
In an effort to develop new strategies for immunotherapy of metastatic renal cell carcinoma, we investigated the therapeutic potential of interleukin-4 in a visceral renal tumor using the murine Renca renal adenocarcinoma model. Renca cells were implanted underneath the renal capsule of Balb/c mice to induce a primary tumor that spontaneously metastasized to several organs. Established primary renal tumors 4 to 6 mm. in diameter were treated by intralesional administration of recombinant murine interleukin-4 (IL-4). This treatment caused a marked inhibition of the primary tumor growth but had little effect on the progression of metastases in the liver, mesentery and lungs. Immunohistochemistry studies performed on renal tumor sections showed a macrophage infiltration that became predominant 7 days after IL-4 treatment. CD8+ T cells were also observed at the periphery and within the tumor. These data suggest that IL-4 mediated a potent antitumor effect when administered intralesionally although its effects remained localized with no impact on metastases at distant sites. Interleukin-4 antitumor activity seems to be mediated by recruitment of macrophages and T cells in the tumor.
Younes
E
E
Department of Urology, Wayne State University School of Medicine, Detroit, Michigan 48201.
Haas
G P
GP
Visscher
D
D
Pontes
J E
JE
Puri
R K
RK
Hillman
G G
GG
D000818:Animals; D002465:Cell Movement; D005260:Female; D015552:Injections, Intralesional; D015847:Interleukin-4 / Q000008:administration & dosage* / Q000627:therapeutic use; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary*; D008264:Macrophages; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D013601:T-Lymphocytes
D011994:Recombinant Proteins; D015847:Interleukin-4