Abstract:
Objective CD4+ CD25+ regulatory T cells (Treg) may contribute to tumor progression by suppressing antitumor immunity. The function of Treg in antitumor immunity regulation in the peritoneal microenvironment of ovarian cancer (OC) was investigated and compared with the circulating Treg to elucidate OC immune escape.
Methods Flow cytometry was used to determine the proportion of CD4+ CD25+ T cells in CD4+ T cells in ascites of 27 patients with OC and in peripheral blood lymphocytes of 28 patients with OC. The samples were analyzed and classified in three stages: primary disease (PD), after chemotherapy (AC), and recurrence disease (RD), according to the clinical conditions of the OC patients upon donating the samples. The percentage of Treg in the three groups was determined in ascites and blood. CD4+ CD25+ T cells were isolated from ascites and peripheral blood of patients with OC using magnetic sorting (MACS) system. The cells were then tested for regulatory function through coculture with carboxyfluorescein diacetate succinimidyl ester-labeled autologous CD4 + CD25- responder cells.
Results The proportion of CD4 + CD25 + T cells in CD4 + T cells significantly increased in ascites (28.25% ± 14.06%) compared with that in blood (14.6% ± 4.74%;P < 0.0001). The Treg in ascites and blood in AC showed higher proportion (P < 0.0001) than those in the PD and RD; the proportion in RD was higher than that in PD (P < 0.0001). Moreover, the Treg in ascites mediated a significantly higher suppression compared with the Treg in peripheral blood (P < 0.001).
Conclusion The frequency and suppressor function of Treg were significantly higher in ascites than in peripheral blood. This finding suggests more possibility for escape immune surveillance in the peritoneal microenvironment. Moreover, the proportion of Treg in AC was higher than that in PD or RD; the proportion in RD was higher than that in the PD. Chemotherapy may favor the expansion of Treg, which may promote the recurrence of cancer.