Serum Containing Inhibitory Factors Which Inhibit Natural Cytotoxicity in Patients With Differentiated Thyroid Cancer

Y Hiromatsu; H Fukazawa; JC How; J Tani; JR Wall

International Journal of Endocrinology and Metabolism

Research Institute for Endocrine Sciences

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Serum Containing Inhibitory Factors Which Inhibit Natural Cytotoxicity in Patients With Differentiated Thyroid Cancer

Author(s):

Y Hiromatsu¹,

H Fukazawa²,

JC How³,

J Tani⁴,

JR Wall^5,*

1First Department of Medicine, Kurume University Medical School, Japan

2South Miyagi Medical Center, Japan

3Department of Medicine, McGill University, Canada

4Department of Medicine, The University of Sydney, Western Clinical School, Nepean Hospital, Australia

5Department of Medicine, The University of Sydney, Western Clinical School, Nepean Hospital, wallj@wahs.nsw.gov.au, Australia

International Journal of Endocrinology and Metabolism:Vol. 3, issue 1; 25-32

Article type:Research Article

Received:Jan 01, 2004

Accepted:Feb 01, 2005

How to Cite:Y HiromatsuH FukazawaJC HowJ TaniJR WallSerum Containing Inhibitory Factors Which Inhibit Natural Cytotoxicity in Patients With Differentiated Thyroid Cancer.Int J Endocrinol Metab.3(1):25-32.

Abstract

Differentiated thyroid cancer (DTC), in which histologic examination often reveals evidence of lymphocytic infiltration at the edges of the tumour, is a good model for the interaction between human cancer and the immunocompetent host immune system.
Materials and Methods: We tested sera from patients with DTC for cytotoxicity against cultured human thyroid, eye muscle and K562 cells in antibody-dependent cell mediated cytotoxicity (ADCC) and natural killer (NK) cell cytotoxicity assays.
Results: When cultured thyroid cells were used as targets in ADCC assay, specific cytotoxicity was increased (% specific lysis> mean + 2SD for normals) in only 2 out of 30 patients with DTC but decreased (% specific lysis < mean + 2SD for normals) in 19 patients and mean for the group was significantly less than that for the normals. The same effect was observed using human eye muscle cells as targets in an ADCC assay. Serum from patients with DTC, but not those from normal subjects, inhibited the ADCC activity against normal thyroid cells in serum from pa-tients with Graves' disease, in a dose dependent manner. Serum from patients with thyroid cancer inhibited natural cytotoxicity against human K562 cells while normal serum did not. Pretreatment of normal PBMC with pooled serum from patients with DTC abolished natural cytotoxicity against K562 cells whereas pooled normal serum had no significant effect.
Conclusion: This phenomenon reflected inhibition of the natural cytotoxicity mediated by (NK) cells in the mixed peripheral blood mononuclear cells (PBMC) population by an unknown serum factor or factors. We confirmed this by performing experiments using sera from patients with DTC, human K562 cells as targets in NK cell assay and PBMC from normal subjects as source of NK cells. The inhibitory factor, which probably works at the level of the NK cells and is called natural cytotoxicity blocking factor (NKBF), may be a marker for invasive thyroid cancer, although this needs to be addressed in further studies.

Keywords

Differentiated thyroid cancer

NK cell cytotoxicity

Antibody-dependent cell mediated cytotoxicity

Host immune response

NK cell blocking factor(s)

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