Antitumor effect of PSK at a distant site: tumor-specific immunity and combination with other chemotherapeutic agents

The antitumor effect of PSK, a Coriolus preparation, was analyzed with the double grafted tumor system in which BALB/c mice received intradermal inoculations of syngeneic Meth-A fibrosarcoma in the right (primary tumor, 10(6) cells) and left (distant tumor, 2 x 10(5) cells) flanks. Intratumoral administration of PSK significantly inhibited the growth of not only the right but also the left tumor. PSK also inhibited the growth of a methylcholanthrene-induced fibrosarcoma BAMC-1, and a methylurethane-induced adenocarcinoma Colon 26 in the double grafted tumor system of syngeneic BALB/c mice. However, when the left distant tumor was different from the right Meth-A tumor, the intratumoral administration of PSK in the right tumor was unable to inhibit the growth of the left BAMC-1 or RL male-1 tumor. The PSK-induced immunity, therefore, is tumor-specific and T lymphocytes may play an important role in antitumor memory function. The enhancement of concomitant immunity by PSK treatment was completely impaired by previous intravenous administration of an alkylating agent, cyclophosphamide (CY). The enhancement of sinecomitant immunity by PSK treatment was also impaired by previous CY intravenous administration. The antitumor effect of PSK was suppressed by previous intravenous administration of another alkylating agent, ACNU. It is possible that alkylating agents suppress the function of effector T cells and granulocytes which are very important for the antitumor immune cascade reaction due to PSK treatment. On the other hand, the antitumor effect of PSK was enhanced by previous intravenous administration of an anti-metabolite, 5-fluorouracil.