The effect of hormone therapy on peripheral blood leukocytic subset distribution in stage D prostatic cancer patients

Abstract

The distribution of mononuclear cell types found in the peripheral blood of patients bearing carcinoma of the prostate were compared by stage and to a control group using monoclonal antibody techniques. Patients with lower stage disease (A, B) had no significant alteration in subset distribution when compared to a control group, while those with higher stage disease (D) had significant deviations. Stage D patients had a decreased representation of helper-inducer T cells and an increased representation of suppressor-cytotoxic T cells, with an overall reduction in the total T cell content. In addition elevated levels of monocytic, granulocytic and null cells were recognized by the polyspecific OKM1 antibody. These differences were in part reversible following hormonal therapy. Such alterations in the ratios between the various T cell populations could be useful in patient staging and treatment selection.

Effect of cyclophosphamide on leukocytic subset distributions in rats carrying the dunning R3327‐MAT‐LyLu prostatic adenocarcinoma

“…Urologic tumors, involving those of the prostate, transitional cells of the bladder, and granular cells of the kidney are immunogenic, provoking lymphocytic infiltration or granulomatous reactions [ 13. Previous reports from our laboratory have shown that patients bearing prostatic cancers have elevated levels of circulating immune complexes [2], specific cell-mediated immunity against homologous tumor extracts [3], and peripheral blood leukocytic subset alterations, which are in part reversible following hormonal therapy [4]. Similar alterations in leukocytic subset distributions have also been identified in other urologic tumors such as renal carcinoma, also in part reversed by therapy [20].…”

“…This is particularly evident in Table I and less clearly so in Table 11. In studies of leukocytic subset distributions within peripheral blood of humans bearing stage D prostate cancer, it was the suppressor-cytotoxic T cells that appeared most sensitive to tumor presence [4]. Cyclophosphamide in this system reduced all T cell populations in both tumor and non-tumor-bearing animals.…”

“…Whether conventional therapies may be augmented with immunotherapy in the treatment of prostate cancer is also an open question. In stage D prostatic cancer patients, T cell subset distributions found within peripheral blood do appear responsive to hormonal manipulations [4], and those suppressor-cyctotoxic T cells recognized by the OKT8 monoclonal antibody also possess receptors for estrogen [24]. The effectiveness of biological response modifiers, such as interleukin-2 administered alone or in combination with hormonal therapy, in restoration of the reduced T cell content and depressed level of cell-mediated immunity found in cancer patients must be examined.…”

“…Data were expressed as the percentage of individual cell representation in accordance with previous reports [4]. Such a method eliminates errors which would result due to differences in yields obtained during spleen cell preparation [4]. Means and standard deviations were determined for each group and the student t-test utilized to determine degree of significance.…”

“…Urologic tumors, including those of the prostate, are immunogenic and frequently provoke lymphocytic infiltration or granulomatous reactions [ 11. In addition, those with prostate cancers have elevated levels of circulating immune complexes [2] ; specific cell-mediated immunity against homologous tumor extracts [3] ; and in stage D patients, alterations in peripheral blood leukocytic subset distributions [4], which are partly reversible following hormonal manipulations. Such leukocytic alterations are greatest in higher stage disease (stages C and D) and are not found in lower stage cases (stages A and B) where the tumor remains encapsulated [4]. The precise mechanisms by which a component immune system and a tumor interact to produce these alterations, as well as their specific roles in anti-tumor responsiveness, remains to be determined.…”