Growth and major histocompatibility antigen expression regulation by IL‐4, interferon‐gamma (IFN‐γ) and tumour necrosis factor‐alpha (TNF‐α) on human renal cell carcinoma

SUMMARY We have recently shown that human renal cell carcinoma (RCC) tumour lines express high‐affinity IL‐4 receptors. Binding of IL‐4 to RCC cells induced a growth inhibition in the range of 20 68%. To enhance the growth inhibitory effect of IL‐4. we have tested the effects of two additional cytok...

Full description

Saved in:
Bibliographic Details
Published in:Clinical and experimental immunology 1994-06, Vol.96 (3), p.476-483
Main Authors: HILLMAN, G. G., PURI, R. K., KUKURUGA, M. A., PONTES, J. E., HAAS, G. P.
Format: Article
Language:English
Subjects:
Animal, plant and microbial ecology
Applied ecology
Biological and medical sciences
Carcinoma, Renal Cell - immunology
Carcinoma, Renal Cell - pathology
Carcinoma, Renal Cell - therapy
Cell Division - drug effects
Cytokines - administration & dosage
Cytokines - pharmacology
Fundamental and applied biological sciences. Psychology
General aspects
Histocompatibility Antigens Class I - metabolism
HLA Antigens - metabolism
HLA-D Antigens - metabolism
Humans
IL‐4
Interferon-gamma - administration & dosage
Interferon-gamma - pharmacology
interferon‐gamma
Interleukin-4 - administration & dosage
Interleukin-4 - pharmacology
Kidney Neoplasms - immunology
Kidney Neoplasms - pathology
Kidney Neoplasms - therapy
Recombinant Proteins
renal cell carcinoma
Tumor Cells, Cultured - immunology
Tumor Cells, Cultured - pathology
Tumor Necrosis Factor-alpha - administration & dosage
Tumor Necrosis Factor-alpha - pharmacology
tumour necrosis factor‐alpha
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:SUMMARY We have recently shown that human renal cell carcinoma (RCC) tumour lines express high‐affinity IL‐4 receptors. Binding of IL‐4 to RCC cells induced a growth inhibition in the range of 20 68%. To enhance the growth inhibitory effect of IL‐4. we have tested the effects of two additional cytokines capable of directly affecting tumour cell growth. IFN‐γ caused a significant inhibition of RCC tumour cell growth (up to 70%) in a dose‐dependent manner, whereas the effect of TNF‐α was more limited (0 20% inhibition). The addition of IL‐4 to IFN‐γ on RCC cells sensitive to lL‐4 induced a greater inhibition of cell growth than that seen with each cytokine alone. IL‐4 and IFN‐γ rendered RCC cells more responsive to the inhibitory effect mediated by TNF‐α, The combination of TNF‐Q with IL‐4 and IFN‐γ induced an optimal growth inhibition (up lo 90 98%) of RCC cells. In addition to a direct anti‐proliferative effect, we have demonstrated that these cytokines can also enhance the expression of MHC antigens on the surface of RCC tumour cell lines which may render the cells more immunogenic, All RCC lines tested expressed class 1 antigens, but not class II antigens. IFN‐γ induced class II expression and up‐regulated the expression of class I antigens on RCC cells. Class II antigen expression was detectable following 48 h incubation, and greater after 72 h with IFN‐7. lL‐4 minimally affected class I expression, whereas TNF‐(v up‐regulated class I antigen expression. IL‐4 or TNF‐α did not induce class II expression. The combination of The three cytokines slightly augmented the up‐regulation of class I and class II antigens observed with IFN‐γ alone. These observations confirm the direct interaction of IL‐4, IFN‐γ and TNF‐a with RCC tumour cells. both at the level of growth regulation and MHC antigen expression, and suggest a therapeutic potential of the combination of the three cytokines for renal ceil carcinoma.
ISSN:0009-9104
1365-2249
DOI:10.1111/j.1365-2249.1994.tb06054.x