Systemic treatment with interleukin-4 induces regression of pulmonary metastases in a murine renal cell carcinoma model

Gilda G. Hillman, Elia Younes, Daniel W Visscher, Esa Ali, John S. Lam, Emily Montecillo, J. Edson Pontes, Gabriel P. Haas, Raj K. Puri

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)257-263
Number of pages7
JournalCellular Immunology
Volume160
Issue number2
DOIs
StatePublished - 1995
Externally publishedYes

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Renal Cell Carcinoma
Interleukin-4
Neoplasm Metastasis
Lung
T-Lymphocytes
Therapeutics
Multiple Pulmonary Nodules
Neoplasms
Injections
Interleukin-5
Lymphocyte Subsets
Granulocytes
Immunotherapy
Immune System
Immunohistochemistry
Macrophages
Antibodies

ASJC Scopus subject areas

  • Immunology
  • Cell Biology

Cite this

Systemic treatment with interleukin-4 induces regression of pulmonary metastases in a murine renal cell carcinoma model. / Hillman, Gilda G.; Younes, Elia; Visscher, Daniel W; Ali, Esa; Lam, John S.; Montecillo, Emily; Pontes, J. Edson; Haas, Gabriel P.; Puri, Raj K.

In: Cellular Immunology, Vol. 160, No. 2, 1995, p. 257-263.

Research output: Contribution to journalArticle

Hillman, Gilda G. ; Younes, Elia ; Visscher, Daniel W ; Ali, Esa ; Lam, John S. ; Montecillo, Emily ; Pontes, J. Edson ; Haas, Gabriel P. ; Puri, Raj K. / Systemic treatment with interleukin-4 induces regression of pulmonary metastases in a murine renal cell carcinoma model. In: Cellular Immunology. 1995 ; Vol. 160, No. 2. pp. 257-263.
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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.",
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