Background: A recent report showed that oral adjuvant immunochemotherapy with protein-bound polysaccharide K (PSK) and tegafur/uracil (UFT) for stage II and III colorectal cancer improves overall survival compared with UFT alone. PSK has been supposed to improve survival through immunological mechanisms such as induction of cytokines, regulation of Th1/Th2 balance, and inhibition of immunosuppressive molecules.
Methods: We investigated the mechanisms by which PSK influences immunological parameters such as Th1 cells (IFN-gamma-positive CD4(+) T cells), Th2 cells (IL-4-positive CD4(+) T cells), Th1/Th2 ratio, NKT cells (CD56(+) T cells and CD57(+) T cells), NK cells, and CD25(+)CD4(+) T cells in stage III gastric cancer patients. Patients were randomly assigned to receive either 3 g PSK plus 300 mg UFT (PSK group) or 300 mg UFT alone (control) orally each day for at least 1 year following their operation.
Results: Twenty-one registered patients with stage III gastric cancer were analyzed. The 3-year overall survival was 62.2% in the PSK group (n = 10) and 12.5% in the control group (n = 11) (P = 0.038). Before operation, there were no significant differences in the proportions of Th1 cells, Th2 cells, Th1/Th2 ratio, CD56(+) T cells, CD57(+) T cells, NK cells, and CD4(+)CD25(+) T cells between PSK and control groups. However, after operation, CD57(+) T cells decreased significantly in the PSK group compared to the control (P = 0.0486). When all patients were analyzed, patients with increased proportion (>18%) of CD57(+) T cells showed worse survival than those with lower (< or = 18%) CD57(+) T cells (3-year survival, 25.0 and 45.7%, respectively; P = 0.046), consistent with our previous report that high CD57(+) is an indicator of poor prognosis in patients with advanced gastric cancer. However, in the group treated with PSK + UFT, 3-year survival of CD57-high patients was as great as that of CD57-low patients (66.7 and 51.4%, respectively; P = 0.67).
Conclusion: The present findings suggest that PSK improves overall survival of stage III gastric cancer patients partly by inhibiting CD57(+) T cells, a proven poor prognostic factor in advanced gastric cancer.