Antitumor Effector Mechanism at a Distant Site in the Double Grafted Tumor System of PSK, a Protein‐bound Polysaccharide Preparation

The antitumor effect at a distant site of PSK, a Coriolus preparation, was analyzed with the double grafted tumor system in which BALB/c mice received simultaneous intradermal inoculations of Meth‐A tumor in the right (10(6) cells) and left (2 × 10(5) cells) flanks and were then injected with PSK in the right‐flank tumor on day 3. PSK inhibited the growth of not only the right but also the left (non‐treated) tumor. Immunized spleen cells were taken from mice which had been cured by the intratumoral administration of 5 mg of PSK and were injected into the Meth‐A tumor on day 3. Adoptive transfer of PSK immunized spleen cells caused the complete regression of Meth‐A tumors. The effector cell activity was lost only after treatment with anti‐Lyt‐1 monoclonal antibody plus complement. Spleen cells and right and left regional lymph node cells prepared from PSK immunized mice were examined for Thy‐1, Lyt‐1, Lyt‐2 and asialo GM1 phenotypes. The number of Lyt‐1‐positive lymphocytes increased in the right regional lymph nodes after intratumoral administration of PSK. A massive accumulation of macrophages and polymorphonuclear leukocytes was found in the right tumor and an infiltration of macrophages and Lyt‐2‐positive lymphocytes was found in the left (non‐treated) tumor by immunohistochemical analyses. These results suggest that intratumoral administration of PSK induces Lyt‐1‐positive cells first in regional lymph nodes, then in the spleen, and subsequently induces macrophages and Lyt‐2‐positive cells in the left (non‐treated) tumor, thus bringing about the regression of metastatic tumors.