title: Systemic treatment with interleukin-4 induces regression of pulmonary metastases in a murine renal cell carcinoma model.
abstract: Advanced metastatic renal cell carcinoma has been shown to be responsive to immunotherapy but the response rate is still limited. We have investigated the therapeutic potential of systemic interleukin-4 (IL-4) administration for the treatment of pulmonary metastases in the murine Renca renal adenocarcinoma model. Renca cells were injected iv in Balb/c mice to induce multiple pulmonary tumor nodules. From Day 5, Renca-bearing mice were treated with two daily injections of recombinant murine IL-4 for 5 consecutive days. IL-4 treatment induced a significant reduction in the number of lung metastases in a dose-dependent manner and significantly augmented the survival of treated animals. Immunohistochemistry studies, performed on lung sections, showed macrophage and CD8+ T cell infiltration in the tumor nodules 1 day after the end of IL-4 treatment. The CD8 infiltration increased by Day 7 after IL-4 treatment. Granulocyte infiltration was not detectable. To clarify further the role of the immune system in IL-4 anti-tumor effect, mice were depleted of lymphocyte subpopulations by in vivo injections of specific antibodies prior to treatment with IL-4. Depletion of CD8+ T cells or AsGM1+ cells abrogated the effect of IL-4 on lung metastases, whereas depletion of CD4+ T cells had no impact. These data indicate that CD8+ T cells and AsGM1+ cells are involved in IL-4-induced regression of established renal cell carcinoma.
authors.affiliation: Department of Urology, Wayne State University School of Medicine, Detroit, Michigan 48201, USA.
authors.forename: G G
authors.initials: GG
authors.lastname: Hillman
authors.forename: E
authors.initials: E
authors.lastname: Younes
authors.forename: D
authors.initials: D
authors.lastname: Visscher
authors.forename: E
authors.initials: E
authors.lastname: Ali
authors.forename: J S
authors.initials: JS
authors.lastname: Lam
authors.forename: E
authors.initials: E
authors.lastname: Montecillo
authors.forename: J E
authors.initials: JE
authors.lastname: Pontes
authors.forename: G P
authors.initials: GP
authors.lastname: Haas
authors.forename: R K
authors.initials: RK
authors.lastname: Puri
mesh_terms: D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D000950:Antigens, Ly / Q000032:analysis; D018414:CD8-Positive T-Lymphocytes / Q000473:pathology; D002292:Carcinoma, Renal Cell / Q000473:pathology / Q000517:prevention & control / Q000556:secondary* / Q000628:therapy; D005260:Female; D005677:G(M1) Ganglioside / Q000032:analysis; D007155:Immunologic Factors / Q000627:therapeutic use*; D015847:Interleukin-4 / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000628:therapy*; D008175:Lung Neoplasms / Q000473:pathology / Q000517:prevention & control / Q000556:secondary*; D008212:Lymphocyte Depletion; D016131:Lymphocyte Subsets / Q000473:pathology; D016246:Lymphocytes, Tumor-Infiltrating / Q000473:pathology; D008264:Macrophages / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D011994:Recombinant Proteins / Q000627:therapeutic use; D018800:Thy-1 Antigens / Q000032:analysis; D013997:Time Factors
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; D000950:Antigens, Ly; D007155:Immunologic Factors; D011994:Recombinant Proteins; D018800:Thy-1 Antigens; D015847:Interleukin-4; D005677:G(M1) Ganglioside; C018835:asialo GM1 ganglioside