In vitro stimulation of tumor-associated immunity in prostatic cancer by levamisole.
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Biomedical subjects
Publications and source records attributed to R A Bhatti.
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The effect of oestrogen (diethylstilboesterol diphosphate, DES-P) on immunity to tumour-associated antigens in patients with prostatic cancer was evaluated by leucocyte adherence inhibition, a suggested in vitro correlate of cellular immunity. Significant (P smaller than 0.05) suppression of immunity to malignant prostate was observed in thirty out of thirty-one patients following pre-incubation of their leucocytes with therapeutically significant levels of DES-P. Suppression of tumour-associated immunity by exogenous oestrogen provides further evidence to earlier studies demonstrating oestrogenic suppression of non-specific cellular responsiveness evaluated by mitogen-induced lymphocytic blastogenesis, and for concern over the efficacy of oestrogenic therapy and its adverse effect in the treatment of patients with hormone-dependent tumours and responsive diseases. The reduced efficiency of immunosurveillance of tumours and underlying infectious agents may contribute to the exacerbation of disease. While speculative, these observations may also be relevant to the possible assocition between uterine cancer and prolonged administration of DES and the development of vaginal tumours in offspring found in association with maternal ingestion during pregnancy.
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Tumor-associated antigen-induced leukocyte adherence inhibition has been used as an in vitro criterion for evaluating the effect of estrogen on cell-mediated antitumor-associated immunity in patients with adenocarcinoma of the prostate. Significant (p less than 0.05) suppression from the reactivity obtained with untreated patients' leukocytes to allogeneic extracts of malignant prostatic tissue ranging from 19 to 80% was observed in all patients following preincubation of their leukocytes with diethylstilbesterol diphosphate. The observed suppression of tumor-associated immunity in the presence of exogenous estrogen provides further evidence to earlier studies that demonstrated estrogenic suppression of nonspecific cellular responsiveness as evaluated by phytohemagglutinin-induced lymphocytic blastogenesis of normal and prostatic cancer patients' lymphocytes and for the initially suggested concern over the efficacy of estrogenic therapy and its adverse effect on host cell-mediated immunological responsiveness.
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Preliminary evidence is presented suggestive of antitumor immunity, cross reactive with allogeneic extracts from tumors of the same type, and serum-blocking factor(s), which appear to be specific to autologous tumor only, in patients with prostatic cancer employing the method of leukocyte adherence inhibition.
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As a possible alternate to existing in vitro assays of cell-mediated host responsiveness to tumour, a modification of the leucocyte adherence inhibition test employing peripheral blood lymphocytes (PBL), has been evaluated in patients with adenocarcinoma of the prostate. PBL from patients with prostatic cancer reacted to varying degrees with 3 M KC1 extracts of autologous and allogeneic prostatic tumours when cultured in the presence of homologous serum. When sensitized PBL and tumour extract were cultured in autologous serum, inhibition ('blocking') of the interaction of PBL and antigen was observed. 'Blocking' was not observed when the tumour extract was allogeneic with respect to the origin of PBL and serum. Cross-reactivity between individual tumours within a given tumour type is in keeping with observations of anti-tumour immunity in patients with other tumours. Observations suggestive of a specificity of 'blocking' for autologous tumour only, is somewhat unique and will require further confirmation. While preliminary, these results provide further evidence suggestive of anti-tumour cell-mediated immunity in prostatic cancer patients previously observed by inhibition of leucocyte migration. The observed 'blocking' effect of autologous serum may be analogous to that observed in the technically more complex colonly inhibition and lymphocyte cytotoxicity tests and may be indicative of one means by which the potential effects of sensitized PBL are inhibited in vivo.