Human ovarian carcinoma: evidence for patient-related differences in susceptibility to cytotoxic effectors that attack different cellular subpopulations within a tumour.
Human ovarian carcinoma cells obtained from ascites were tested for susceptibility to lysis by peripheral blood NK cells, alpha-interferon-activated NK cells, and interleukin 2-activated killer cells. Cryopreserved tumour cell preparations were used to allow repeated testing of the same target, and the tumour cells were fractionated using albumin density gradients to determine if fractions containing clonogenic (stem) cells were killed. Four tumour cell donors were studied and each showed a different pattern of susceptibility of unfractionated tumour to lysis by different effector cells. Using fractionated tumour cells, we found that NK and interferon-activated NK cells did not always lyse cells in the clonogenic fractions and that interferon activation could in some cases shift killing away from the clonogenic fractions and towards the peak of proliferating (but not self-renewing) colony forming cells. Interleukin 2-activated killer cells (LAK) however, killed the fractions containing clonogenic cells in all 4 cases. The magnitude of killing seen when fractions of the original tumour were tested were often striking when compared to lysis of the unfractionated cells. Apparent heterogeneity between patients and stem cell susceptibility to effector cells may be important determinants of the efficacy of treatment of patients with biologic response modifiers such as interferon and interleukin 2.
Clark
D A
DA
Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
Hirte
H W
HW
Buick
R N
RN
D002469:Cell Separation; D003602:Cytotoxicity, Immunologic; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation; D010051:Ovarian Neoplasms / Q000276:immunology*; D014407:Tumor Cells, Cultured / Q000276:immunology; D014410:Tumor Stem Cell Assay
D007376:Interleukin-2