RECONSTITUTION OF ANTITUMOR EFFECTS OF LENTINAN IN NUDE-MICE - ROLES OF DELAYED-TYPE HYPERSENSITIVITY REACTION TRIGGERED BY CD4-POSITIVE T-CELL CLONE IN THE INFILTRATION OF EFFECTOR-CELLS INTO TUMOR

Lentinan, an antitumor polysaccharide used clinically in Japan, requir es the intact T cell compartment to manifest its antitumor effects. Th e aim of the current study was to clarify the mechanisms playing cruci al roles in the T cell requirement in the expression of antitumor effe cts of lentinan. Lentinan treatment of BDF1 mice transplanted intrader mally with FBL-3 induced complete tumor regression and a marked increa se in survival time. The antitumor action of lentinan was abolished in mice treated simultaneously with antibodies to CD4 and CD8 antigens, whereas antibody to CD4, CD8 or NK1.1 alone was ineffective. The natur al killer, cytotoxic T lymphocyte, and helper T cell activities were a lready augmented in this FBL-B/BDF1 system and thus further augmentati on of these activities by lentinan was not observed. These activities did not correlate with the antitumor activity of lentinan, as was conf irmed in lymphocyte subset depletion experiments. On the contrary, the delayed-type hypersensitivity (DTH) response against tumor-associated antigens was triggered by lentinan and was abrogated only in mice tre ated simultaneously with antibodies to CD4 and CD8 antigens. Furthermo re, a non-cytolytic tumor-associated antigen-specific CD4(+) T cell cl one able to induce the DTH response in concert with lentinan reconstit uted the antitumor effects in B6 nude mice when administered with lent inan. These results suggest that, in addition to the augmentation of i mmune effector cell activity against tumors, infiltration of these cel ls into the tumor burden initiated by the DTH responses at tumor sites may be involved in eradication of tumors by lentinan.