Lysis of Fresh Human Tumor Cells by Autologous Peripheral Blood Lymphocytes and Tumor‐infiltrating Lymphocytes Activated hy PSK

The protein‐bound polysaccharide PSK was tested for the ability to induce in vitro autologous tumor killing (ATK) activity in human cancer patients. Peripheral blood lymphocytes (PBL) and tumor‐infiltrating lymphocytes (TIL) demonstrated various levels of cytotoxicity against autologous, freshly isolated tumor cells. When PBL and TIL were cultured overnight with PSK, ATK activity was induced in previously non‐reactive cases and augmented in previously reactive samples. The PSK effect was observed with PSK concentrations of 10–100 μg/ml that could be obtained in the blood of cancer patients who received standard oral administration of PSK. The manifestation of PSK‐induced ATK required active cell metabolism and RNA and protein syntheses, but not DNA synthesis of lymphocytes. PSK‐induced enhancement of ATK was not abrogated by monoclonal antibodies (mAb) directed against interferon (IFN)α or IFNγ‐. In addition, mAb that neutralized interleukin‐2 (IL‐2) or mAb reactive with α‐chain or β‐chain of IL‐2 receptors (IL‐2R) had no effect on PSK‐induced ATK activity. Supernatants from PSK‐stimulated lymphocyte cultures did not induce ATK. Cell fractiona‐tion experiments revealed that CD3(‐)CD16(+) large granular lymphocytes (LGL) and/or CD3(+)CD16(‐) T lymphocytes were responsible for both spontaneous and PSK‐induced ATK. PSK‐activated LGL, but not T lymphocytes expressed lysis of fresh allogeneic tumor cells. These results indicate that PSK activates PBL and TIL to exhibit ATK independently of IL‐2/IL‐2R systems.