Cellular immune defects in patients with melanoma involving interleukin-2-activated lymphocyte cytotoxicity and a serum suppressor factor.
Interleukin-2 (IL-2) can stimulate human blood lymphocytes to acquire tumor cytotoxicity, designated as lymphokine-activated killer (LAK) cytotoxicity. In 29 of 33 patients with melanoma, LAK cytotoxicity could be induced with recombinant IL-2 against fresh (noncultured) autologous and/or allogeneic melanoma cells. There was an excellent correlation of LAK cytotoxicity with the clinical stage of disease when the cells were incubated with medium containing IL-2 plus 10% fetal calf serum (p = 0.003). The 14 patients with localized melanomas (group I) had the same level of specific lysis as did 16 normal controls (24% versus 25%). Eleven patients with resectable regional or distant metastases (group II) had a lower level of cytotoxicity compared with normal controls (16% vs 25%), while those with unresectable distant metastases (group III) had the lowest level of cytotoxicity compared with controls (9% versus 25%). When aliquots of lymphocytes from the same patients were cultured with 10% autologous human serum, the levels of LAK cytotoxicity were even lower in patients with localized melanoma and resectable metastases compared with normal controls (15% and 9%, respectively, versus 27% for controls; p = 0.0007). This was due to a serum suppressor factor that inhibited the induction of cytotoxic activity in LAK precursors. The level of cytotoxicity in these patients increased to baseline levels after surgery and the serum suppressor factor disappeared in six of the seven patients in whom it was present before surgery. Thus induction of LAK cytotoxicity requires IL-2, decreases with advancing stages of disease, and is inhibited by a serum suppressor factor related to tumor growth.
D003602:Cytotoxicity, Immunologic; D006023:Glycoproteins / Q000097:blood*; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000276:immunology*; D007376:Interleukin-2 / Q000502:physiology*; D007694:Killer Cells, Natural / Q000276:immunology; D008213:Lymphocyte Activation; D008545:Melanoma / Q000276:immunology* / Q000601:surgery; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins
D006023:Glycoproteins; D007376:Interleukin-2; D009363:Neoplasm Proteins; C038588:serum immunosuppressive factor, human