Rashid A. Bhatti

Leukocyte adherence inhibition and immunoreactivity in prostatic cancer. I. Identification of anti-tumour cell-mediated immunity and "blocking" factor.

Abstract Modification of the recently described leukocyte adherence inhibition (LAI) test was utilized for the evaluation of anti-tumour cell-mediated immunity and the identification of “blocking” factor in 20 patients with prostatic cancer. Evidence of cross-reactivity of the observed anti-tumour immunity with extracts prepared from tumours of the same type and the specificity of “blocking” of the reactions for autologous sensitized lymphocytes and tumour only have similarly been demonstrated employing the LAI test. While the observed cross-reactivity between individual tumours, within each tumour type is in keeping with observations of anti-tumour immunity in patients with other tumours, e.g., colon, breast and melanoma, observations suggestive of a specificity of “blocking” for autologous tumour only is perhaps somewhat unique, of which further studies will be needed to confirm.

Immunosuppression of cell- and serum- mediated tumour-associated immunity in prostatic cancer by human seminal plasma

Abstract The immunosuppressive properties of the hormonal and/or secretory milieu or tumour-elaborated factors (in the case of carcinoma) of the prostate have been hypothesized as contributory to the natural history of prostatic cancer. The effect of normal human seminal plasma (HuSPl) on immunity to tumour-associated antigens and the ‘arming’ of normal peripheral blood leukocytes (PBL) by cytophilic antibody in the sera of patients with prostatic cancer have been evaluated by leukocyte adherence inhibition, a suggested in vitro correlate of cellular immunity. Significant (P

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

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 alpha2-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 alpha2-globulin, while significantly elevated within each stage, as compared with the 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 alpha2 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 alpha2 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.

Leukocyte adherence inhibition and immunoreactivity in prostatic cancer. II. Tissue- and disease-specificity of anti-tumour cell-mediated immunity

Abstract Tissue- and disease-specificity of the reactivity of peripheral blood leukocytes from 20 prostatic cancer patients to malignant prostatic tissue have been evaluated. Results of leukocyte adherence inhibition, employed previously, had suggested antitumour cell-mediated immunity. Absence of significant reactivity in prostatic cancer patients to tissues other than malignant prostate and in non-prostatic cancer patients (including patients with benign disease of the prostate) to malignant prostate confirms earlier observations. These had suggested the identification of prostatic tumour-associated antigens and of tumour-associated immunity in prostatic carcinoma.

Cell-mediated immunity in prostatic cancer and its diagnostic relevancy

Cell-mediated immunity (CMI) in prostatic cancer patients to presumptively identified prostatic tumour-associated antigens (TAA) was further evaluated in this study by tube leukocyte adherence inhibition in 504 patients with and without prostatic cancer. Peripheral blood leukocytes from 210 of 312 (67%) prostatic cancer patients possessed significant reactivity to extracts of malignant prostate. However, significant reactivity to malignant prostate was also observed in 89 of 192 (46%) controls comprised of patients with other than carcinoma of the prostate [including 91 patients with benign prostatic hypertrophy of which 46 (51%) possessed significant reactivity to malignant prostate] and healthy adults. With the exception of a significant difference in the reactivity between stage A vs stage C patients, there was no significant correlation between the level of reactivity to malignant prostate and the stage of disease. Had CMI to presumptively identified prostatic TAA been employed as an adjunctive diagnostic criterion to detect prostatic cancer, 191 (38%) of the 504 patients in this study would have been incorrectly diagnosed. The results of this study emphasize the critical need in attempting to delineate tumour-directed immunity from possible concomitant sensitization to tissue- and species-specific antigens for the identification, isolation and physicochemical characterization of what previously have been referred to as presumptively or putatively identified prostatic TAA.

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.