The influence of cyclophosphamide on antitumor immunity in mice bearing late-stage tumors.

Spleen cells from mice bearing late-stage methylcholanthrene-induced tumor did not show any tumor activity when mixed with tumor cells in Winn's assay. Treatment of these mice with cyclophosphamide (CY) induced a tumor-inhibitory activity in spleen, occurring on day 7 after treatment, reaching its maximum on day 11 and disappearing by day 21. This antitumor activity could not be induced in control, tumor-free or T-deficient tumor-bearing mice. CY-induced tumor-inhibitory activity was immunologically specific, and mediated by Thy-1+, L3T4-, Ly-2+ cells. Contrary to spleen cells from untreated tumor-bearing mice, spleen cells from CY-treated tumor-bearing mice did not suppress the antitumor activity of immune spleen cells in Winn's assay. However, in contrast to immune spleen cells, CY-induced tumor-inhibitory cells did not manifest antitumor activity when transferred systemically (i.v.) into T-cell-deficient tumor-bearing mice. Even more, spleen cells from CY-pretreated mice, harvested 7-15 days after the drug administration, partially suppressed the antitumor activity of concomitantly transferred spleen cells from specifically immune mice. Nevertheless, CY-pretreated mice manifested concomitant immunity, i.e. these mice exhibited higher resistance to a second inoculum of the same tumor than did nontreated mice or even mice with excised primary tumor.

Production of prostaglandin E by squamous carcinoma of the head and neck and adenocarcinoma of gastrointestinal tissue.

The production of prostaglandin E ex vivo was studied in samples of 31 squamous cell carcinomas of the head and neck (SCCHN) and 12 adenocarcinomas of gastrointestinal tract (ACGI). As a control, the PGE production was measured in 22 samples of noninvolved mucosa in patients with SCCHN and 12 samples of gastrointestinal mucosas. The mean PGE production by SCCHN was significantly higher than in normal mucosa. Furthermore, the PGE production by tumors which recurred or spread to regional lymph node within 18 months after surgery was higher than in tumors which did not recur within that interval. Also, production of PGE by noninvolved mucosa was significantly higher in patients in which tumor recurred after surgery than in patients which were tumor free. On the other hand, the mean production of PGE by ACGI was not different from that of normal mucosa. These data show that determination of PGE production might have prognostic significance in SCCHN.