Evaluation of Cellular Immunologic Responsiveness in the Clinical Management of Patients with Prostatic Cancer

Abstract

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.

Evaluation of Cellular Immunologic Responsiveness in the Clinical Management of Patients with Prostatic Cancer

“…Thus, in an attempt to evaluate the presence of host responsiveness to tumour in patients with prostatic can cer, the applicability of the method of direct migration inhibition of leuco cytes from prostatic cancer patients to pooled allogeneic extracts of nor mal, benign and malignant prostatic tissue has been investigated. With ex ception of preliminary communications from this laboratory employing inhibition of leucocyte migration (1LM) [4,5] and of the use of antigeninduced leucocyte adherence inhibition [6][7][8], there are few, if any, stud ies of in vitro cellular immunity to prostatic tissue.…”

“…These investigations have evaluated lymphocytic blastogenesis to PHA in prostatic cancer patients prior to [ 1 ] and followine therapy [ …”

Immunotherapy for Prostatic Cancer

“…Although, other explanations for clinical evidence suggestive of an immunologic response to a prostatic tumor-specific or TAA following cryoprostatectomy are tenable, the subsequent failure to identify tumor-specific or TAA would be somewhat surprising. In this regard, preliminary studies demonstrating a differential response between leukocytes from patients with prostatic cancer to extract preparations o f allogeneic and autologous pros tatic tissue and normal prostatic tissue as evaluated by inhibition o f leukocyte migration (39,40) and the presence of cytotoxic lymphocytes in patients with prostatic cancer (41) are suggestive o f cellular sensitivity to malignant tissue antigens.…”

“…Here, the elaboration of leukocyte inhibitory factor from lymphocytes sensitized in situ to malignant prostatic tissue as evaluated by the inhibition of leukocytes from patients with prostatic cancer in the presence o f allogeneic or autologous prostatic tissue (39,40) and recent evidence o f the presence o f cytotoxic 'killer' lymphocytes in patients with prostatic cancer (41 ) may offer added credence to this approach.…”

Migration-Inhibitory Effect of Serum from Patients with Prostatic Cancer

“…Leukocyte migration was carried out by a modification of the method of Bendixen and So boro [10] as recently detailed [11]. In brief, leukocytes were resuspended to a final con centration of 70 x 106 cells/ml.…”