Effect of estrogen on tumor-associated immunity in patients with adenocarcinoma of the prostate.

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.

Arming of normal leukocytes with sera from patients with adenocarcinoma of the prostate.

A tumor-associated antigen-induced leukocyte adherence inhibition assay was used to evaluate the effect of serum from patients with adenocarcinoma of the prostate on the antitumor reactivity of normal leukocytes. Peripheral blood leukocytes from 53 normal (control) subjects were armed with serum from 22 patients with localized (Stage A) and metastatic (Stage D) prostatic cancer and reacted with allogenic extract of malignant prostate as specific tumor-associated antigen. Leukocytes pre-treated with serum from patients with Stage A cancer show significantly stronger responses to malignant prostate than do those pretreated with serum from patients with Stage D cancer, which induced little or no response. This may be attributed to an "arming factor" present in the sera of patients with an initial stage of prostatic cancer which appears to be capable of sensitizing normal leukocytes and making them specifically reactive to tumor extract. The specificity of arming with individual and pooled patient's sera was delineated by the use of extracts from other genitourinary tumors.

Immunoregulatory markers in rats carrying Dunning R3327 H, G, or MAT-LyLu prostatic adenocarcinoma variants.

The Dunning R3327 tumor represents a system for studying prostate cancer in Copenhagen X Fischer rats. Animals bearing variant sublines (H, G, and MAT-LyLu) differing in growth rate, differentiation, hormone responsiveness, and metastatic ability were assayed for three immunological markers. Spleens were passed through a tissue sieve, and mononuclear cells were obtained by Ficoll-Hypaque centrifugation. These were assayed for leukocytic subsets using monoclonal antibodies. An adherent population was isolated and evaluated using thin-layer chromatography for conversion of radiolabeled arachidonic acid to E series prostaglandins. Finally, sera from these animals were assayed for levels of circulating immune complexes using polyethylene glycol precipitation. Data from 52 rats bearing the various tumors were obtained, correlated with subline aggressiveness, and compared to 15 controls. Each tumor group demonstrated significantly lower helper/suppressor T-cell ratios than controls, probably due to general tumor presence. In addition, the most aggressive R3327 MAT-LyLu variant had significantly increased prostaglandin E synthesis by adherent spleen cells compared to the H or G sublines and significantly increased levels of circulating immune complexes relative to the H subline. G subline values for both prostaglandin E and circulating immune complexes levels were intermediate, suggesting that these markers correlate better with tumor aggressiveness than helper/suppressor T-cell ratios.

Serum immunoglobulin E in pemphigus.

Immunoglobulin E levels in the sera of patients with pemphigus (12 with Brazilian pemphigus foliaceus (BPF) and 11 with pemphigus vulgaris (PV)) were determined by means of a solid phase radioimmunoassay. A significant increase in IgE level was observed in BPF patients compared to the level of IgE in PV patients and healthy adults. The implications of an elevated level of IgE with respect to other aberrations of immunologic responsiveness and the suggested infectious etiology of BPF are considered.

Effect of human seminal plasma on tumour-associated immunity in patients with adenocarcinoma of the prostate.

Tumour-associated antigen-induced leukocyte adherence inhibition has been used as an in vitro criterion for evaluating the effect of normal human seminal plasma (HuSePl) on cell-mediated anti-tumour-associated immunity in patients with adenocarcinoma of the prostate. Significant (P < 0.01) suppression from the reactivity obtained with unincubated patients' leukocytes to allogenic extracts of malignant prostatic tissue ranging from 16 to 80% was observed in 22 of 25 patients (88%) following preincubation of their leukocytes with HuSePl. The observed suppression of tumour-associated immunity in the presence of HuSePl provides further evidence for the suppressive activity of SePl on a range of in vitro immune response in normal murine and human hosts. It is suggested that these results, together with those demonstrating experimental prostatic cancer from sensitization by spermatozoa and the relationship of prostatic cancer to repression of sexual activity, provide preliminary evidence of the possible participation of SePl as contributory to the natural history of prostatic cancer.

Carcinoembryonic antigen test in renal cell carcinoma.

CEA (carcinoembryonic antigen) determinations were performed on 203 blood and urine samples from 23 patients with renal cell carcinoma. Neither the blood nor the urine CEA test was able to confirm the diagnosis or predict the status of the disease in more than one half of these patients. As presently constituted, the CEA test is not accurate for the diagnosis or prognosis of renal cell carcinoma.

Effect of hormone therapy on immune response in patients with prostatic cancer.

Thirty-one patients with adenocarcinoma of the prostate had laboratory studies done for total proteins, serum immunoglobulins, white blood cell counts, lymphocyte blastogenesis, skin tests, acid phosphatase, and CEA (carcinoembryonic antigen). The 16 patients receiving no hormones had depressed total proteins, lymphocyte and monocyte counts, skin tests, and CEA compared with the 15 patients receiving hromones who had depressed serum immunoglobulins, white blood cell counts, lymphocyte blastogenesis, and acid phosphatase.

Serum proteins in prostatic cancer. II. Effect on in vitro cell-mediated immunologic responsiveness.

The sera from patients with prostatic cancer have been observed to posses an unidentified factor capable of inhibiting the migration of leukocytes and the proliferative response to the nonspecific mitogen, phytohemagglutinin. Observation of inhibition of these two suggested in vitro correlates fo cell-mediated immunologic responsiveness emphasizes (1) the importance to the adjunctive diagnosis and prognosis of patients with malignancy of identifying the presence of abnormal serum proteins, and (2) the role of humoral inhibitory or "immunoregulatory" factors as potential abrogators of mechanisms of host resistance, for example, immunologic surveillance, and thus the degree to whcih the host may respond to his tumor.

Immunostaging in carcinoma of prostate.

Immunostaging is a new method of assessing patients immunologically before and after immunotherapy. Twenty-eight patients with adenocarcinoma of the prostate were immunostaged independently by two investigators. There was a positive correlation between both immunostagings. There was also a positive correlation between the patient's immunostage and the clinical stage of his cancer.

Inhibition of leukocyte migration by extracts of malignant prostatic tissue and correlation of degree of in vitro sensitization to clinical responsiveness in prostatic cancer patients.

In an attempt to evaluate the degree of in vitro cellular sensitization to tumor and its relationship to clinical responsiveness, direct leukocyte migration tests were carried out in patients with varying degrees of adenocarcinoma of the prostate employing pooled allogeneic extracts of normal, benign, and malignant prostatic tissue as a source of antigen. Cell-mediated immunity to presumably common prostatic tumor associated antigens was observed. The degree of sensitization of clinically significant specific reactivity of the patients' leukocytes to malignant prostatic tissue was greatest in patients with localized disease, low-grade tumor, and clinically inactive disease than in patients with advanced disease, high-grade tumor, and clinically active disease. Evaluation of the possible correlation of specific reactivity to malignant prostatic tissue as a prognostic index of clinical responsiveness revealed a positive correlation with the degree of sensitization in 3 (43 per cent) of 7 patients. Correlation in 4 patients was questionable because of observations of "stimulation" of migration rather than inhibition, suggested by some to be reflective of weak sensitization to tumor. Evaluation of a larger patient population as well as a prospective study of the relationship of the degree of sensitization and clinical responsiveness will be necessary before any definitive conclusions may be drawn regarding the present observations.

Responsiveness of lymphocytes to soluble extracts of prostatic tumors and abrogation by serum-blocking factor(s).

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.

Effect of transfer factor on tumor-associated immunity and tumor growth of the Dunning R-3327G rat prostate adenocarcinoma.

Of importance in the design and application of improved or new modalities of treatment are their evaluation on relevant animal models. In the case of prostate cancer (PCa) the Dunning R-3327 rat prostate adenocarcinoma (PCa), and its variant sublines, is one such experimental tumor model of its human counterpart. In a preliminary study, the effect of transfer factor (TF), one form of passive immunotherapy, on tumor-associated immunity (TAI) and tumour growth and histology of the G subline (a poorly differentiated, fast-growing, androgen sensitive, and poorly metastatic tumour of the Dunning R-3327 rat PCa) has been evaluated. TF prepared from the leukocytes of tumor-bearing animals and nontumor-bearing animals referred to as sensitized (STF) and unsensitized (UTF), respectively, had no significant effect on TAI or tumor size. The only noticeable effect of TF in this study was the presence of variable and moderate lymphocytic infiltrates, necrosis, and degenerative-type cells in tumors of animal recipients of STF. The failure to observe significant differences in TAI among tumor bearing and nontumor bearing animals raises doubt in part, of the immunogenicity of the G subline tumor and its appropriateness, at least for subsequent immunological studies. Further factors considered in this regard, are questions of tumor load, including the possible need for the use of adjuvant, and the parameters and sensitivity of immune responsiveness selected for evaluation and immunocompetency. Subsequent evaluation of the effect of TF on other more immunogenic variant sublines of the Dunning R-3327 rat tumor may yet provide further and more useful information.

Immunobiology of the Dunning R-3327 rat prostate adenocarcinoma sublines: plasma and tumor effusion prostaglandins.

Enhanced production of prostaglandins (PGs) by experimentally-induced and naturally occurring tumors and their effect on tumor growth and immunosurveillance have been noted. Directed toward further evaluation of the relationship between prostatic tumor growth and its milieu, i.e., microenvironment, we investigated the possible correlation between levels of PGs, tumor size, and metastatic potential. For this purpose, the levels of PGE2 and PGF2 alpha in plasma and tumor effusions of three tumor sublines of the Dunning R-3327 rat prostate adenocarcinoma were measured: R-3327H, well-differentiated, slow-growing, and poorly metastatic; R-3327G, poorly differentiated, fast-growing, and poorly metastatic; and R-3327 Mat LyLu, anaplastic, fast-growing, and highly metastatic. The level of PGF2 alpha was highly variable with no significant differences being noted between the tumor sublines. The mean values of PGF2 alpha were, however, higher, although not significantly so, in the smaller tumors within each of the sublines. The levels of PGE2 were significantly higher in Mat LyLu effusions than those from the nonmetastasizing R-3327G and H sublines. Evaluation and comparison of the relationship between tumor burden, i.e., size versus levels of PGE2 and PGF2 alpha showed no significant differences. A vasodilator and regulator of immunological responsiveness, PGE2, may function as a modulator of tumor metastases. In consonance with studies by others elevated levels of PGE2 may possibly serve as a prognostic marker for the high metastatic potential of neoplastic cells.

Impotence therapy and cancer of the prostate.

Prostate cancer developed in two male patients being treated with fluoxymesterone for erectile impotence. It is suggested that the current increased interest in and therapy for sexual dysfunction be accompanied by an awareness of a possible causal relationship between exogenous androgens and prostrate cancer.

Adjuvant immunotherapy (BCG) in stage D prostate cancer.

Thirty-three patients with advanced prostate cancer were prospectively randomized to receive either Bacillus Calmette-Guerin (BCG) adjuvant immunotherapy plus conventional therapy or conventional therapy alone. Conventional therapy consisted of estrogens or observation. There was a statistically significantly (p less than 0.05) longer survival in the 16 BCG-treated patients (42 weeks) than in the 17 control patients (29 weeks).

Alterations in host responsiveness in patients with prostatic cancer following cryosurgery or transurethral resection.

Anesthesia, stress, trauma or the operation per se have been reported to result in alterations of host resistance in a wide range of diseases. The effect of such changes on the thymolymphatic system of patients with prostatic cancer is not known. While evaluating in vitro parameters of cellular immunologic responsiveness in patients with prostatic cancer, we have observed a depression two to seven days following cryosurgery or transurethral resection (TUR) of the proliferation of phytohemagglutinin (PHA)-stimulated peripheral blood lymphocytes (PBL). Contrary to the reduced proliferation 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 proliferation, particularly if involving tumor-cloned T-cells, may provide reduced surveillance to potential metastatic tumor cells leading to an alteration of tumor-host homeostasis. The potential of reduced surveillance, at least in the case of TUR, appears to be supported by observations that patients dying from prostatic cancer at our institution had an antecedent TUR. Identifying those patients with changes in responsiveness before surgery, as well as those prone to develop or undergo further reductions in responsiveness after surgery, would appear to be relevant in the management of patient with prostatic as well as other malignancies. Pre- and/or postoperative immunotherapy in such patients may be indicated.