Polysaccharide preparation PSK augments the proliferation and cytotoxicity of tumor-infiltrating lymphocytes in vitro.
Polysaccharide preparation PSK augments the proliferation and cytotoxicity of tumor-infiltrating lymphocytes in vitro.
复制标题
多糖制剂 PSK 可增强体外肿瘤浸润淋巴细胞的增殖和细胞毒性。
作者：
K. Noguchi;H. Tanimura;H. Yamaue;T. Tsunoda;M. Iwahashi;M. Tani;S. Mizobata;T. Hotta;K. Arii;M. Tamai
我们研究了多糖制剂PSK是否直接增强肿瘤浸润淋巴细胞（til）的增殖和细胞毒性。从10例胃肠道肿瘤患者（胃癌5例、结肠癌3例、胰腺癌2例）中分离TILs。用IL-2和PSK培养til 7天。用100微克/毫升PSK孵育后，TILs的DNA合成增强，这与癌症患者口服PSK的血清水平相似。PSK在DNA合成中的作用也通过消除非t细胞被发现。此外，我们建立了TIL克隆，并研究了PSK对TIL克隆的影响。在没有非t细胞的CD4阳性和CD8阳性TIL克隆中，PSK增强了DNA合成，表明PSK直接作用于TIL。我们通过4 h和16 h 51Cr释放试验检测TILs的细胞毒活性。在4小时51Cr释放实验中，PSK对TILs对自体肿瘤细胞和KATO-III细胞的细胞毒活性没有影响，而在16小时51Cr释放实验中，PSK诱导TILs对自体肿瘤细胞的高裂解率。我们使用双室平板研究了PSK诱导TILs细胞因子的能力。与不加PSK的TILs相比，加PSK的TILs混合肿瘤细胞培养上清液对肿瘤细胞DNA合成的抑制作用更大。提示PSK通过诱导细胞毒性细胞因子诱导til的长期杀伤活性。因此，PSK在没有T细胞和非T细胞相互作用的情况下增强了TILs的增殖反应，并诱导了TILs的细胞毒性细胞因子。
We have investigated whether or not polysaccharide preparation PSK directly augments the proliferation and cytotoxicity of tumor-infiltrating lymphocytes (TILs). TILs were separated from 10 patients with gastrointestinal cancer (5 gastric cancers, 3 colon cancers and 2 pancreatic cancers). TILs were cultured with IL-2 and PSK for 7 days. The DNA synthesis of TILs was augmented by incubation with 100 micrograms/ml of PSK, which was similar to serum level with oral administration of PSK in cancer patients. The effect of PSK in DNA synthesis was also found by elimination of non-T cells. Furthermore, we established TIL clones and examined the effect of PSK on TILs clones. The DNA synthesis was augmented by PSK in CD4 positive and CD8 positive TIL clones without non-T cells, suggesting that PSK acts directly on TILs. We examined the cytotoxic activities of TILs by the 4-h and 16-h 51Cr release assay. PSK did not affect the cytotoxic activity of TILs against autologous tumor cells and KATO-III cells in the 4h 51Cr release assay, whereas PSK induced high lysability of TILs against autologous tumor cells in the 16-h 51Cr release assay. We studied the ability of PSK to induce cytokines from TILs using a double chamber plate. The DNA synthesis of tumor cells was more suppressed by the mixed-tumor cell culture supernatants of TILs cultured with PSK, compared to that of TILs cultured without PSK. It is suggesting that PSK induced long term killing activity of TILs by induction of cytotoxic cytokines. Thus, PSK augmented the proliferative response of TILs without interaction of T cells and non-T cells and induced cytotoxic cytokines of TILs.