The antitumor effect of PSK, a Coriolus preparation, at a distant site was analyzed with the use of a double grafted
tumor system in which male BALB/c mice received simultaneous intradermal inoculations of Meth-A
tumor in the right (10(6) cells) and the left (2 x 10(5) cells) flanks and were then injected with PSK in the right
tumor on the third day thereafter. The antitumor effect of intratumoral administration of PSK in the right
tumor on days 3, 4 and 5 was compared with the effect of surgical resection of the right
tumor on day 5. Three out of 8 mice given PSK intratumorally became
tumor-free whereas no mouse
tumor-free in the left flank was found among the surgically resected mice. As regards sinecomitant immunity,
tumor inoculation into the right flank followed by intra-tumoral administration of PSK on days 3 and 5 and surgical excision of the primary
tumor on day 6 resulted in complete rejection of a
tumor challenge in the left flank on day 21. The combination of presurgical intratumoral
injections of PSK (more than 2 times) and postoperative
oral administration of PSK appeared to be most effective in eradicating secondary
tumors. Isolated TILs (tumor-infiltrating lymphocytes), obtained from the right
tumor (treated with PSK) and the left
tumor on day 10 in the double grafted
tumor system were cultured in RPMI1640 with 10%
fetal calf serum for 24 h. The culture supernatants were harvested and tested for the presence of chemotactic activity for neutrophils or macrophages. Significant
neutrophil chemotactic factor (NCF) and
macrophage chemotactic factor (MCF) activities were detected in the
culture media from PSK-treated TILs that had been cultured for 24 h. Neither significant neutrophil nor macrophage chemotactic activity was detected in the media from untreated TILs. NCF and MCF activities were also detected in the culture supernatant from PSK-treated
tumor tissue on day 6. PSK-induced NCF in the murine
tumor was neutralized by treatment with anti-human
IL-8 IgG, and might be murine IL-8-like factor. Therefore, neutrophil and macrophage infiltrations of
tumors following intratumoral
injections of PSK are probably mediated by inductions of IL-8-like factor and MCF.