Elsevier

Cytokine

Volume 7, Issue 2, February 1995, Pages 118-129
Cytokine

Regular Article
Synergistic Effects of IL-6 and IFN-γ on Carcinoembryonic Antigen (CEA) and HLA Expression by Human Colorectal Carcinoma Cells: Role for Endogenous IFN-β

https://doi.org/10.1006/cyto.1995.1016Get rights and content

Abstract

When administered as single agents, both interferon gamma (IFN-γ) and interleukin 6 (IL-6) significantly increase carcinoembryonic antigen (CEA) and HLA class I antigen expression on the surface of human colorectal tumour cells. Studies were carried out to determine whether by combining those cytokines a synergistic enhancement of CEA and HLA expression could result. The findings revealed that the administration of 20 units IFN-γ along with 1.7 ng IL-6, concentrations of each cytokine that individually induced minimal antigenic changes, together synergistically increased CEA and HLA class I as well as induced qualitative changes in HLA expression on WiDr human colon carcinoma cells. The magnitude of the synergistic increases in CEA and HLA class I expression were reminiscent of the level of antigen augmentation observed when administering 20- to 100-fold higher amounts of each cytokine as a single agent. Also, the addition of IL-6 potentiated the IFN-γ induction of HLA class II expression. The combined administration of IL-6 potentiated the IFN-γ did not have any additive or synergistic effects on the growth suppression of those tumour cells. Interestingly, utilization of specific neutralizing antibodies for type I interferons abrogated the increases of CEA and HLA expression seen with IL-6 treatment alone or in combination with IFN-γ. Moreover, reverse transcriptase/polymerase chain reaction analyses revealed a constitutive expression as well as a temporal increase of IFN-β mRNA transcripts in colon tumour cells treated with IL-6. Therefore, the findings provide indirect evidence that IFN-β production seems to play a critical role in the ability of IL-6 to upregulate antigen expression alone or in combination with IFN-γ. These findings provide insight into cytokine combinations that synergistically upregulate tumour-associated and normal HLA antigen expression on the surface of human tumour cells. Those results provide the rationale for the combined use of such cytokines to heighten tumour cell recognition in monoclonal antibody- or cell-mediated-based immunotherapeutic approaches.

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