Kariya Y, Okamoto N, Fujimoto T, Inoue N, Kihara T, Sugie K, Yagita M, Kanzaki H, Mori T, Uchida A
Department of Late Effect Studies, Kyoto University.
Jpn J Cancer Res. 1991 Sep;82(9):1044-50. doi: 10.1111/j.1349-7006.1991.tb01941.x.
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 micrograms/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) alpha or IFN gamma. In addition, mAb that neutralized interleukin-2 (IL-2) or mAb reactive with alpha-chain or beta-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 fractionation 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.
对蛋白结合多糖PSK进行了测试，以检验其在人类癌症患者中诱导体外自体肿瘤杀伤（ATK）活性的能力。外周血淋巴细胞（PBL）和肿瘤浸润淋巴细胞（TIL）对新鲜分离的自体肿瘤细胞表现出不同程度的细胞毒性。当PBL和TIL与PSK过夜培养时，在先前无反应的病例中诱导出了ATK活性，而在先前有反应的样本中则增强了该活性。在接受标准口服PSK的癌症患者血液中可获得的10 - 100微克/毫升的PSK浓度下观察到了PSK效应。PSK诱导的ATK表现需要淋巴细胞的活跃细胞代谢以及RNA和蛋白质合成，但不需要DNA合成。针对干扰素（IFN）α或IFNγ的单克隆抗体（mAb）不会消除PSK诱导的ATK增强作用。此外，中和白细胞介素 - 2（IL - 2）的mAb或与IL - 2受体（IL - 2R）的α链或β链反应的mAb对PSK诱导的ATK活性没有影响。PSK刺激的淋巴细胞培养上清液不会诱导ATK。细胞分级分离实验表明，CD3 - CD16 +大颗粒淋巴细胞（LGL）和/或CD3 + CD16 - T淋巴细胞负责自发的和PSK诱导的ATK。PSK激活的LGL而非T淋巴细胞表现出对新鲜同种异体肿瘤细胞的裂解作用。这些结果表明，PSK激活PBL和TIL以独立于IL - 2/IL - 2R系统表现出ATK。
