Horizontal studies of cell mediated immune reactions to autologous tumour antigens in patients with operable mammary carcinoma

Abstract

Summary.-The leucocyte migration and guinea-pig macrophage migration procedures were used to assess cell mediated, tumour directed immune reactions in patients with mammary carcinoma undergoing simple mastectomy with or without post-operative irradiation. Forty-seven per cent of patients reacted to autologous tumour antigens and 40o% to allogeneic antigens when tested 7 days after operation; 23% reacted to autologous antigens at 2 months, 19% at 6 months and 34%0 at 1 year after surgery. Reactions to benign tissue fractions were rare. Better discrimination between test and control subjects was obtained when 3000 g sediments rather than nuclei-depleted homogenates (extracts) were used. Irradiation 3-7 weeks postoperatively did not depress the in vitro response at 2 months and yielded a higher rate of positive reactions at 6 months. Correlations of serial LMT responses with certain clinical findings are discussed.

Mechanisms of leucocyte migration inhibition by breast tumour cell fractions

“…We (Jones and Turnbull, 1975). McCoy et al (1974) have improved still further on our rate of approximately 5000 patients positive at 7 days after simple mastectomy: using 3M KCI extracts of breast tumours, significant leucocyte migration inhibition was obtained in 20/26 (770o) pre-or immediately postsurgery breast cancer patients.…”

“…It was previously shown that serial postoperative measurements of tumourdirected leucocyte migration inhibition in breast cancer patients may be of relevance to the understanding of the complex host-tumour interrelationship and may provide information of clinical significance (Jones and Turnbull, 1975;Jones et al, 1976). This paper has tried to confirm that the in vitro response to particulate tumour-derived antigenic material is mediated by cellular immune mechanisms and thus permit interpretation of the clinical correlations observed in breast cancer patients.…”

“…THE leucocyte migration test (LMT) of S0borg and Bendixen (1967) has been successfully employed in studies of tumour-directedimmuneresponses inpatients with breast cancer (Andersen et al, 1970;Cochran et al, 1974;Turnbull, 1974, 1975;McCoy et al, 1974); malignant melanoma (Cochran, Jehn and Gothoskar, 1972;McCoy et al, 1975); hypernephroma (Kjaer, 1974); and various other tumours (Wolberg, 1971;Segall et al, 1972). Significant discrimination between patients and controls was achieved, and the possibility exists that this simple and reproducible assay might be of considerable value in the clinical assessment of patients with cancer.…”

“…Alternative mechanisms thought to be operative under certain circumstances included reactions between antigens and cytophilic antibodies on the surface of leucocytes (Packalen and Wasserman, 1971;Rocklin, 1974) and the direct action of antigen on sensitized granulocytes (Senyk and Hadley, 1973 Preparation of tumour cell fractions.-The preparation of particulate extracts from malignant breast tumours has been fully described elsewhere (Jones and Turnbull, 1975). Briefly, tissue obtained at operation was minced and disrupted using a douncetype hand homogenizer and the homogenate centrifuged at 1000 g to remove nuclei.…”

“…Cell migration tests.-Migration inhibition tests were performed using a semi-micro method developed specifically to utilize minimal quantities of tumour cell fractions and which was previously shown to give a high degree of reproducibility (Jones and Turnbull, 1975). Tumour extracts at 100 and 200 jg/ml in TC 199 + 10% foetal calf serum (FCS), tumour 3000 g fraction at 100 and 200 Hg/ml, and control medium TC 199 + 10 % FCS without antigen were added to consecutive wells of the Sterilin migration chamber.…”