Humoral cytotoxicity in melanoma patients and its correlation with the extent and course of the disease

Abstract

Complement-dependent cytotoxicity against melanoma cells was demonstrated with a microassay in sera from melanoma patients. The response was tumor-specific and histologic type-specific since 16 out of 52 (30%) melanoma patient sera taken before surgery reacted against melanoma cells, whereas 3 out of 43 (7%) control sera, collected from patients with unrelated tumors and from cancer-free individuals, were positive. The serum activity correlated with the clinical stage of the disease since it was detected in 15 out of 40 patients with stage I and II tumors and in 1 of the 12 patients in stage III. Twelve melanoma patients, clinically tumor-free for to 4 years after surgery, showed no humoral cytotoxicity. A follow-up study of 13 melanoma patients revealed that the cytotoxicity appeared 7-10 days after radical removal of the tumor and that it disappeared if there was no recurrence. The histologic type-specificity was further tested by assaying sera from 16 melanoma and 10 breast-cancer patients simultaneously on both melanoma and breast-cancer cells; a positive reaction was observed in 6 cases of melanoma and in 5 of breast cancer on homologous cells only, in 1 case on the opposite type of cells, and in 3 cases on both types of tumor cells.

Characterization of human malignant melanoma cell lines. III. Membrane immunofluorescence reactivity with sera from patients with melanoma

“…In the light of our own personal experience and the results of the workshop on cytoplasmic immunofluorescence tests referred to above, it is of interest that the three reports of non-specificity of serological reactions in melanoma have been with the cytoplasmic antibody system. Most studies using allogeneic target cells are similar to ours and report higher reactivity of melanoma sera against melanoma targets than normal sera (Morton et al, 1968;Nairn et al, 1972;Cornain et al, 1975;Whitehead, 1973;Shiku et al, 1976;Canevari et al, 1975;Romsdahl and Cox, 1970), although very few authors have examined sera from other cancer patients (Cornain et al, 1975;Wood and Barth, 1974). A number of authors report that with increasing spread of disease, antibody reactivity disappears (Lewis et al, 1969;Morton et al, 1968;Nairn et al, 1972;Bodurtha et al, 1975;Bourgoin and Bourgoin, 1973;Dellaporta et al, 1973;Canevari et al, 1975).…”

“…Again, the retention of some allogeneic specificity as demonstrated by us and by others (Morton et al, 1968;Nairn et al, 1972;Cornain et al, 1975;Whitehead, 1973;Canevari et al, 1975;Romsdahl and Cox,, 1970), indicates that continuous cultures of tumor cells: may still be useful as substrates for assays of antigen-antibody reactions in the study of human tumor immunity. Further studies with an expanded panel of cell fines and cross absorption of test sera may lead to a better appreciation of the nature and diversity of human melanoma-specific antigens.…”

“…Bourgoin and Bourgoin (1973) report increased reactivity against cell lines as opposed to fresh autologous cells, but fail to giw~ supportive specificity data. Dellaporta et al (1973) and Canevari et al (1975) have presented evidence that irL a cytotoxic antibody system, cell lines gave specific reactivity with melanoma sera as compared to normal control sera. Whitehead (1973) also reports similar specificity for cytoplasmic fluorescent antibody studies on cell lines.…”

“…However, we have not performed experiments to look for this in our patients with advanced disease. Some studies suggest that minimal disease or prolonged disease-free intervals are associated with decreased reactiv-ity (Morton et al, 1968;Dellaporta et ai., 1973;Whitehead, 1973;Canevari et al, 1975), indicating that recent or strong antigenic stimulation is necessary for a sustained antibody response.…”

Report of a workshop on the immune response to solid tumours in man

“…Although the cytotoxicity was low, the simplicity of the system augurs well for studies of specificity and correlation with clinical state (Canevari et al, 1975).…”