Inhibition of leukocyte migration by human thyroid adenocarcinoma associated antigens

Abstract

Abstract. The agarose microdroplet leukocyte migration inhibition (LMI) assay was used successfully to demonstrate the existence of cell-mediated immunity to tumour-associated antigens (TAA) in patients with thyroid adenocarcinoma. With the use of crude tumour extracts obtained from a mixed papillary-follicular adenocarcinoma of the thyroid by hypertonic KCl solubilization, 50.0% positive reactivity was observed in metastatic thyroid cancer patients, whereas no healthy donors or patients with auto-immune thyroid disease showed a positive response in the LMI assay. Among responders, no antigenic cross-reactivity was found between the crude tumour extracts and non-cancerous antigens such as human thyroglobulin, or extracts of Graves' disease thyroid tissue, or kidney tissue. The crude tumour extracts were fractionated by Sephadex G-200 chromatography and the effluent materials were pooled into three fractions. The high molecular weight fraction corresponding to the side of thyroglobulin elution, and the intermediate molecular weight fraction, showed no TAA activity. The low molecular weight fraction including substances of molecular size near that of ovalbumin (45 000 molecular weight) selectively retained the TAA activity. TAA activity in the low molecular weight fraction was concentrated in comparison to the crude tumour extracts. When this fraction was tested in the LMI assay, positive reactivity increased in metastatic thyroid cancer patients, but no response was observed in either healthy donors or patients with thyroid auto-immune diseases. The LMI response to TAA was more striking in patients with active metastatic cancer than in those whose metastatic foci had responded to treatment.