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.
Direct immunofluorescent staining of specimens of accessory sexual gland tissue and of coagulo-prostatic fluid, a normal secretory product of the coagulating and prostate glands of the male rabbit with fluorescein-labelled goat anti-rabbit IgG antiserum revealed localization of IgG within the folds of the submucosal stroma of acini of the coagulating and prostate glands. Binding of IgG to secretory granules within the lumina of these glands and presumably to these same granules seen in preparations of smears of coagulo-prostatic fluid was also seen. Similar immunofluorescent staining of the seminal vesicles disclosed localization of IgG to the stroma and faint intercellular or cytoplasmic fluorescence of glandular epithelial cells.The possible implications of these findings relative to the development of autoantibodies to accessory sex gland tissues and fluids of the male rabbit and the means of acquisition of IgG by these tissues and fluids are discussed.
Evaluation of alterations in the level of the five major electrophoretic fractions of serum proteins (albumin, α1- a2-, β- and γ-globulin) in 18 patients with prostatic cancer prior to and following cryoprostatectomy disclosed: (i) a progressive increase in the level of α2- and β-globulin and the incidence of patients possessing statistically significant (p < 0.05) elevations in these proteins with a progression of the stage of their malignancy; (ii) a significant decrease in albumin, α2- and β-globulin and increase in α1- and γ-globulin from their preoperative levels following cryoprostatectomy in patients with metastatic disease (stage III) in association with a favorable clinical response; (iii) an overall significant decrease in albumin and α2-globulin and increase in α1-globulin from their preoperative levels, and (iv) a general association of decreases in albumin (83% of the patients) and α2-globulin (92%) and increases in α1-globulin (92%) and γ-globulin (75%) with a favorable clinical response following cryoprostatectomy. Limited to study of a small patient population, the present results confirm earlier studies suggestive of a prognostic potential for α2-globulin, as applied to stage identification in prostatic cancer once the initial diagnosis has been made. Pending confirmation and evaluation of a larger patient population, the observed alterations in serum proteins, while not pathognomonic for prostatic cancer, and alterations of inhibitory (‘immunoregulatory’) factors, may provide adjunctive criteria for monitoring the clinical response following cryoprostatectomy.
Levels of the three major serum immunoglobulins (G, A, M) were quantitated prior to and up to 2 weeks following each of two independent freezing treatments of the primary prostatic tumour in 4 patients undergoing remission or healing of their metastatic lesions. Cyclical alterations in the level of IgG accompanied by moderate alterations in the level of IgA were noted post-operatively. Most striking was an almost twofold increase in the level of IgM in 3 of the 4 patients evaluated. While possibly a non-specific association, observations of increased levels of IgG and IgM following cryotherapy may represent an active immunologic response by the host to prostatic tissue (tumour?)-specific or tumour-associated antigen(s) in the form of ‘blocking’ factor(s) or cytotoxic antibody.
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