Shimizu Y, Watanabe A, Whiteside T L
Third Department of Internal Medicine, Toyama Medical and Pharmaceutical University, Japan.
J Hepatol. 1992 Sep;16(1-2):197-202. doi: 10.1016/s0168-8278(05)80115-1.
The phenotypic characteristics of freshly isolated tumor-infiltrating lymphocytes (TIL) obtained from human liver tumors were analyzed by two-color flow cytometry. TIL consisted of mainly CD3+ T-lymphocytes (70-80%). The ratio of CD4/CD8 in TIL from primary and metastatic liver tumors and autologous peripheral blood lymphocytes (A-PBL) was 1.3, 1.1 and 1.3, respectively. The majority of CD3+ T-lymphocytes (mean +/- SD; 95 +/- 11%) expressed T-cell antigen receptor (TCR) alpha/beta, and gamma/delta TCR positive T-cells were only 5 +/- 4.5% in TIL from both primary and metastatic liver tumors. TIL showed significantly higher percentages of transient activation markers, such as CD25 (Tac) and HLA-DR, than A-PBL. TIL also contained significantly more populations of CD3+ CD45RO+ T-lymphocytes, which are considered to be expressed on primed (memory) T-lymphocytes, than A-PBL. Furthermore, TIL from primary liver tumors demonstrated significantly higher percentages of CD3+ CD45RO+ T-cells than those from metastatic liver tumors. These data indicate that TIL from human liver tumors are an apparently distinct population from A-PBL, and that local immune responses against human primary and metastatic liver tumors might be different. Moreover, TIL from primary liver tumors consisted of mainly activated or primed (memory) T-cells, suggesting that they were sensitized and activated by autologous tumor cells in vivo. These observations may imply the possibility of adoptive immunotherapy using TIL against human primary liver tumors.
采用双色流式细胞术分析了从人肝癌中新鲜分离的肿瘤浸润淋巴细胞(TIL)的表型特征。TIL主要由CD3 + T淋巴细胞组成(70 - 80%)。原发性和转移性肝癌的TIL以及自体外周血淋巴细胞(A - PBL)中CD4/CD8的比例分别为1.3、1.1和1.3。大多数CD3 + T淋巴细胞(均值±标准差;95±11%)表达T细胞抗原受体(TCR)α/β,原发性和转移性肝癌的TIL中γ/δ TCR阳性T细胞仅占5±4.5%。与A - PBL相比,TIL显示出更高比例的瞬时激活标志物,如CD25(Tac)和HLA - DR。TIL中CD3 + CD45RO + T淋巴细胞的数量也显著多于A - PBL,CD3 + CD45RO + T淋巴细胞被认为在致敏(记忆)T淋巴细胞上表达。此外,原发性肝癌的TIL中CD3 + CD45RO + T细胞的比例显著高于转移性肝癌。这些数据表明,人肝癌的TIL与A - PBL明显不同,并且针对人原发性和转移性肝癌的局部免疫反应可能存在差异。此外,原发性肝癌的TIL主要由活化或致敏(记忆)T细胞组成,这表明它们在体内被自体肿瘤细胞致敏和激活。这些观察结果可能意味着采用TIL对人原发性肝癌进行过继性免疫治疗的可能性。