Yoo Y K, Heo D S, Hata K, Van Thiel D H, Whiteside T L
Department of Medicine, University of Pittsburgh School of Medicine, Pennsyvania.
Gastroenterology. 1990 Feb;98(2):259-68.
Tumor-infiltrating lymphocytes and autologous peripheral blood lymphocytes from 7 patients with adenocarcinoma of the colon were evaluated for expansion and antitumor activities during culture in the presence of 1000 U/ml of recombinant human interleukin 2. Functional and phenotypic characteristics of tumor-infiltrating lymphocytes and autologous peripheral blood lymphocytes were compared between weeks 2 and 3 of culture in recombinant interleukin 2. All but one tumor-infiltrating lymphocyte and all autologous peripheral blood lymphocyte preparations proliferated well in vitro. Tumor-infiltrating lymphocytes expanded better (p less than 0.05) than autologous peripheral blood lymphocytes, reaching median-fold expansions of 2231 (range 1-4720) and 108 (range 13-1263), respectively. Cytotoxicity of interleukin 2-activated tumor-infiltrating lymphocytes and autologous peripheral blood lymphocytes against fresh autologous or allogeneic colon carcinoma targets was relatively low in these cultures. Due to better proliferation, tumor-infiltrating lymphocytes showed significantly greater (p less than 0.05) total cytotoxic activity per culture against fresh autologous tumor-cell targets than did autologous peripheral blood lymphocytes, achieving a median total lytic units of activity per culture of 671 compared with 92 for autologous peripheral blood lymphocytes. Cytotoxicity was not restricted to autologous tumor cells. Two-color flow cytometry demonstrated that the predominant proliferating cell population in interleukin 2-expanded long-term cultures of tumor-infiltrating lymphocytes and autologous peripheral blood lymphocytes expressed the CD3+Leu19- phenotype. Some cultures were enriched in CD3+ Leu19+ and CD3-Leu19+ cells. This study indicated that tumor-infiltrating lymphocytes from most but not all human primary colon adenocarcinomas could be expanded in the presence of recombinant interleukin 2 and mediate non-major histocompatibility complex-restricted antitumor cytotoxicity. Because fresh colon carcinoma cells appear to be resistant to in vitro lysis by interleukin 2-activated tumor-infiltrating lymphocyte and autologous peripheral blood lymphocyte effectors, the role of adoptive immuno-therapy in treatment of advanced colon carcinomas in humans may have to be reevaluated.
对7例结肠癌患者的肿瘤浸润淋巴细胞和自体外周血淋巴细胞进行评估，观察其在含有1000 U/ml重组人白细胞介素2的培养基中培养时的扩增情况和抗肿瘤活性。在重组白细胞介素2培养的第2周和第3周，比较肿瘤浸润淋巴细胞和自体外周血淋巴细胞的功能和表型特征。除1份肿瘤浸润淋巴细胞制剂外，所有肿瘤浸润淋巴细胞制剂和所有自体外周血淋巴细胞制剂在体外均增殖良好。肿瘤浸润淋巴细胞比自体外周血淋巴细胞扩增得更好（p<0.05），其扩增倍数中位数分别为2231（范围1 - 4720）和108（范围13 - 1263）。在这些培养物中，白细胞介素2激活的肿瘤浸润淋巴细胞和自体外周血淋巴细胞对新鲜自体或同种异体结肠癌靶细胞的细胞毒性相对较低。由于增殖情况更好，肿瘤浸润淋巴细胞每培养物对新鲜自体肿瘤细胞靶标的总细胞毒性活性显著高于自体外周血淋巴细胞（p<0.05），每培养物的总裂解单位活性中位数为671，而自体外周血淋巴细胞为92。细胞毒性并不局限于自体肿瘤细胞。双色流式细胞术显示，在白细胞介素2扩增的肿瘤浸润淋巴细胞和自体外周血淋巴细胞长期培养物中，主要的增殖细胞群表达CD3 + Leu19 - 表型。一些培养物中富含CD3 + Leu19 + 和CD3 - Leu19 + 细胞。本研究表明，大多数（但并非全部）人类原发性结肠腺癌的肿瘤浸润淋巴细胞在重组白细胞介素2存在的情况下能够扩增，并介导非主要组织相容性复合体限制的抗肿瘤细胞毒性。由于新鲜结肠癌细胞似乎对白细胞介素2激活的肿瘤浸润淋巴细胞和自体外周血淋巴细胞效应细胞的体外裂解具有抗性，因此可能需要重新评估过继免疫疗法在人类晚期结肠癌治疗中的作用。
