Whiteside T L, Miescher S, Hurlimann J, Moretta L, von Fliedner V
Cancer Immunol Immunother. 1986;23(3):169-78. doi: 10.1007/BF00205646.
T lymphocytes were isolated from tumor biopsies in 13 patients with breast carcinomas. Immunohistology with monoclonal antibodies confirmed the presence of mononuclear cell infiltrates composed primarily of T lymphocytes in all tumors studied. While the proportion of T lymphocytes expressing the T4 or the T8 surface marker varied from tumor to tumor as determined by morphometric analysis, T8+ cells were more numerous than T4+ cells in 8/12 breast tumors studied. Relatively few T cells (less than 10% in 11/12 tumors) were in an activated state as judged by the surface expression of HLA-DR antigens or the receptor for interleukin-2 (IL-2). In 1 case 20% of the infiltrating mononuclear cells were expressing the IL-2 receptor. The tumor infiltrating lymphocytes (TIL) recovered from 10 tumors were cloned in a microculture system that permits proliferation of nearly 100% of normal peripheral blood T lymphocytes (PBL-T). In contrast to normal and autologous PBL-T, frequencies of proliferating T lymphocyte precursors (PTL-P) were depressed (less than 0.01) in 7/10 TIL preparations indicating a decreased responsiveness of TIL to phytohemagglutinin at the single-cell level. The frequency of PTL-P was noticeably higher in 2 cases (0.03 and 0.09) and close to normal in 1 case (0.39). A total of 170 clones were expanded in vitro and analyzed for different functional capabilities. Most of these clones expressed the T4+/T8-phenotype (73%) and strikingly 53% of these T4+/T8- clones were cytolytic in a lectin-dependent assay, a functional subset which is uncommon among normal PBL-T. Some clones (10%) lysed allogeneic breast tumor cells (MCF7). Only 15% of the clones displayed natural killer activity. Among the cytolytic clones, 17 of 31 tested were also IL-2 producers irrespective of the T4 or T8 phenotype. Our results show that human mammary carcinomas contain many infiltrating T cells with cytolytic potential. Interestingly, among the proliferating cytolytic T cell clones (56% of the microcultures), many expressed the T4+/T8- phenotype. These findings may indicate that the in situ cytolytic reaction (against unknown antigens) is associated preferentially with class II antigens.
从13例乳腺癌患者的肿瘤活检组织中分离出T淋巴细胞。用单克隆抗体进行免疫组织学检查证实，在所有研究的肿瘤中均存在主要由T淋巴细胞组成的单核细胞浸润。形态计量分析表明，不同肿瘤中表达T4或T8表面标志物的T淋巴细胞比例各不相同，但在研究的12例乳腺癌中，有8例T8 +细胞比T4 +细胞多。根据HLA - DR抗原或白细胞介素-2（IL - 2）受体的表面表达判断，处于活化状态的T细胞相对较少（12例肿瘤中有11例少于10%）。在1例中，20%的浸润单核细胞表达IL - 2受体。从10例肿瘤中回收的肿瘤浸润淋巴细胞（TIL）在一种微培养系统中进行克隆，该系统能使近100%的正常外周血T淋巴细胞（PBL - T）增殖。与正常和自体PBL - T相比，7/10的TIL制剂中增殖性T淋巴细胞前体（PTL - P）的频率降低（小于0.01），表明TIL在单细胞水平对植物血凝素的反应性降低。在2例中PTL - P的频率明显较高（0.03和0.09），1例接近正常（0.39）。共170个克隆在体外扩增，并分析其不同的功能能力。这些克隆中的大多数表达T4 + /T8 - 表型（73%），其中53%的T4 + /T8 - 克隆在凝集素依赖性试验中具有细胞溶解活性，这是正常PBL - T中不常见的功能亚群。一些克隆（10%）能裂解同种异体乳腺癌细胞（MCF7）。只有15%的克隆具有自然杀伤活性。在具有细胞溶解活性的克隆中，31个经检测的克隆中有17个也是IL - 2产生者，与T4或T8表型无关。我们的结果表明，人类乳腺癌含有许多具有细胞溶解潜力的浸润性T细胞。有趣的是，在增殖性细胞溶解T细胞克隆中（微培养物的56%），许多表达T4 + /T8 - 表型。这些发现可能表明原位细胞溶解反应（针对未知抗原）优先与II类抗原相关。
