Cellular cytotoxicity in vitro in transitional cell carcinoma of the human urinary bladder: ⁵¹Cr‐release assay

Abstract

The cytotoxicity in vitro of peripheral blood lymphocytes from 54 patients with transitional cell carcinoma of the urinary bladder (TCC-bladder) against a small panel of allogeneic target cells was studied by the "'Cr-release assay. Lymphocytes f r o m 20 patients with other neoplastic diseases, mainly urogenital cancers, were used as controls. Also included were lymphocytes from 24 healthy donors. Lymphocytes f r o m individual donors of all three groups were frequently cytotoxic t o any one of the target cell types on the panel and occasionally this cytotoxicity was high. However, lymphocytes f r o m TCC-bladder patients who were untreated for their disease had an elevated mean cytotoxicity against cells from t w o different cell lines of TCC-bladder origin as compared with that against other target cells, derived either from normal bladder epithelium, from colon qarcinoma o r from malignant melanoma. The cytotoxicity against TCC-bladder targets of lymphocytes from the clinical controls (who were untreated for their cancer) was not significantly elevated over that against the other targets. The same was true for the healthy donors. Lymphocytes f r o m TCC-bladder patients treated with radiotherapy f r o m 1-12 years before testing also had an elevated mean cytotoxicity against TCCbladder targets. This group (31 patients) was heterogeneous, comprising patients with a generally reduced cytotoxicity and others whose lymphocytes were strongly cytotoxic t o TCC-targets. However, while no correlations between cytotoxlcity t o TCCbladder targets and targets of other origin were seen for the untreated patients, the treated TCC-bladder patients showed a positive correlation between cytotoxicity t o TCC-bladder targets and normal " bladder targets. Taken together, the results indicate that lymphocytes of most (but not all) donors was selective, i.e. individual donors' lymphocytes were cytotoxic for some target cell types but not for others. Inspection of cytotoxicity profiles suggests that these selective reactions reflect multifactorial immune responses against a variety of antigens. In addition, in TCC-bladder patients there exists a superimposed cytotoxicity, probably reflecting reactions against one o r several tumor-associated antigens. In treated patients this may be masked by a higher incidence o f cross-reactions, o r by a generally suppressed reactivity. Finally, the results also emphasize the importance of using age-and sexmatched controls for assessing the relative cytotoxicity of different groups of lymphocyte donors.

Lymphocyte‐mediated lysis of tumor cells in vitro (ADCC), induced by serum antibodies from patients with urinary bladder carcinoma or from controls

“…As already stated, this was not an unexpected finding since the treated TCC patients studied here were a heterogeneous group. In this respect, the results obtained with IgG from either treated or untreated TCC patients are very similar to those obtained in previous studies of the cytotoxicity of their lymphocytes (Troye et al, 1977a;1980a).…”

“…The cells were propagated in Parker's medium 199, supplemented with glutamine, streptomycin, penicillin and 10 % heat-inactivated fetal bovine serum (FBS). For details, see Troye et al (1977a;1980a). All sera used for preparing IgG were fractionated either immediately after withdrawal from the donor or after a few days' storage at 4" C. No frozen sera were used.…”

“…Superimposed on this, lymphocytes from TCC patients exhibit a disease-related cytotoxicity (Bean et al, 1975), probably reflecting the recognition of one or several TCC-associated antigens (Troye et al, 1977a(Troye et al, 1980a.…”

Spontaneous cell-mediated cytotoxicity in patients with transitional cell carcinoma of the urinary bladder

“…Although impairment of SLMC in cancer patients has been reported by some investigators [2,7,19,31], others have found these functions normal [8,17]. Selective enhancement of SLMC against certain target cells has also been reported [2,14,32]. Our results indicate that PBL from patients with TCC did not exhibit a decline in overall spontaneous cytotoxic activity compared with lymphocytes of a control group.…”

“…This observation has since been supported by a number of authors [1,15,32]. This in vitro cytotoxicity is, to a certain extent, influenced by tumor mass and various treatments.…”