The effect of oestrogen, cryosurgery and transurethral resection (TUR) of the prostate on the blastogenic response of thymic-dependent peripheral blood lymphocytes (PBL) to the non-specific mitogen, phytohaemagglutinin (PHA) was evaluated as one in vitro criteria of each of these treatment modalities on the cellular immunologic responsiveness of 24 patients with prostatic cancer. A depression 5 days following receipt of oestrogen and 2–7 days following cryosurgery or TUR of the responsiveness of PHA-stimulated PBL was observed. Oestrogen-induced aberrations of responsiveness may not only be of relevance in prostatic cancer patients, but also to the suggested association between uterine cancer and prolonged administration of diethylstilboesterol and the development of vaginal tumours in offspring found in association with maternal ingestion during pregnancy. Particularly striking was that contrary to the reduced responsiveness of PBL cultured in autologous and homologous serum from patients receiving TUR, patients receiving cryosurgery, while also showing reduction in autologous serum, showed increased responsiveness when cultured in homologous serum. Although transient, depression of lymphocyte responsiveness, particularly if involving tumour-cloned T cells, may provide reduced surveillance to potential metastatic tumour cells leading to an alteration of tumour-host homeostasis. The potential of reduced tumour surveillance at least in the case of TUR, appears to be supported by observations that patients expiring from prostatic cancer at our institution had an antecedent TUR. The possibility of identifying those patients possessing aberrations of responsiveness prior to therapy, as well as those prone to develop or undergo further reductions in their responsiveness following the presently evaluated treatment modalities would appear to be of real and relevant concern in the management of the patient with prostatic, as well as other types of malignant neoplasms. The possibility of pre-operative and/or post-operative immunotherapy in such patients may be indicated pending further study.

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Host cellular responsiveness to tumour was evaluated in 37 patients with varying degrees of clinically active and inactive adenocarcinoma of the prostate by direct inhibition of leucocyte migration (ILM) employing saline extracts of pooled allogeneic normal, benign and malignant prostatic tissue as a source of antigen. The majority of these patients had received or were receiving conventional therapy at the time of evaluation. 13 (35%) prostatic cancer patients possessed clinically significant specific reactivity to malignant prostatic tissue, whereas only 1 (8%), of 13 control patients (11 healthy adults and 2 patients with carcinoma other than of the prostate: bladder and penis) possessed comparable reactivity. While the wide range of specific reactivity observed overall, including ‘stimulation’ of migration, compared with the mean percent ILM was very large, the SD of the mean specific percent ILM in the 13 prostatic cancer patients possessing clinically significant specific reactivity to malignant prostatic tissue, was most respectable. Since all reactions were allogeneic, these results indicated that prostatic cancer patients possessed cell-mediated immunity to presumably common prostatic tumour-associated antigens. Further evaluation disclosed that the incidence of patients possessing clinically significant reactivity to malignant tissue was almost identical regardless of the patient’s stage of malignancy, histological grade of tumour, or clinical status. The degree of sensitization of clinically significant reactivity to malignant tissue was, however, greater in patients with localized disease, low grade tumour, and clinically inactive disease, than in patients with advanced disease, high grade tumour, and clinically active disease. Evaluation of the possible correlation of specific reactivity to malignant prostatic tissue as a prognostic index of subsequent clinical responsiveness revealed a positive correlation with the degree of sensitization in 3 (43%) of 7 patients available for routine follow-up. Correlation in four patients was questionable due to the observations of ‘stimulation’ of migration rather than inhibition. While providing initial preliminary evidence of the presence of cell-mediated anti-tumour immunity in patients with prostatic cancer and promise of a possible prognostic index, the wide range in the variability of cellular responsiveness and the failure to identify clinically significant reactivity to malignant prostatic tissue in the majority (65%) of the patients evaluated, raises concern as to whether ILM employing saline extracts will provide the necessary in vitro assay of cellular responsiveness for the evaluation of prostatic cancer patients.

Thymic-dependent lymphocytic blastogenesis of peripheral blood lymphocytes of 59 patients with varying stages of prostatic cancer to the non-specific plant mitogen, phytohaemagglutinin (PHA) and the correlation of their responsiveness with the clinical stage of malignancy and level of α₂-globulin have been evaluated. Patients within each of the four stages of malignancy possessed statistically significant extrinsic (noted in 40 (68%) of 59 patients) and intrinsic (noted in 21 (47%) of 45 patients) aberrations of their lymphocytic responsiveness to PHA compared with the responsiveness of a control population of non-cancer patients. The observed aberrations were, however, not significantly different between each stage nor did they correlate with the stage of disease. Similarly, levels of α₂-globulin, while significantly elevated within each stage, as compared with levels in the control population, no significant differences or correlation with the stage of disease was observed. Of interest, perhaps pending further study, were observations of the increased frequency of the number of patients with a significant elevation of α₂ with a progression of malignancy from localized to invasive and metastatic disease. A similar trend in the incidence of the association of aberrations of lymphocytic reactivity with elevated levels of α₂ were also noted with a progression of disease. The present confirmatory observations of a recent study in this laboratory of diminished cellular responsiveness in patients with prostatic cancer may be of considerable relevance in directing the therapeutic management of the patient – lest the therapy selected be further debilitating providing reduced surveillance – metastization of tumour cells, and alteration of tumour-host homeostasis.