Kooi S, Zhang H Z, Patenia R, Edwards C L, Platsoucas C D, Freedman R S
Department of Gynecologic Oncology, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Cell Immunol. 1996 Dec 15;174(2):116-28. doi: 10.1006/cimm.1996.0301.
This study was carried out to determine whether HLA class I or class II expression on ovarian tumor cells and lymphocytic infiltration of the epithelial ovarian carcinoma (EOC) tissues were responsible for the ability to expand tumor-infiltrating lymphocytes (TIL) in vitro in low concentrations of recombinant interleukin-2 (rIL-2). Immunohistochemical analysis was performed using monoclonal antibodies that recognize framework determinants of either HLA class I or HLA class II or leukocyte differentiation antigens (LCA, CD3, CD4, and CD8). Cryostat sections of EOC had HLA class I and HLA class II expression on at least 5% of tumor cells in 18 of 20 specimens (90%). From another portion of the same tumor specimens T-cell lines were developed from TIL in low concentrations of rIL-2 (200-600 IU/ml) in 7 of 17 patients. Tumors from which TIL were expanded in vitro with rIL-2 had significantly higher proportions of HLA class I-positive tumor cells (73 +/- 10%) compared to tumors from which TIL failed to grow (40 +/- 10%) (P = 0.036). However, there was no difference in the proportions of HLA class II-positive tumor cells between the two groups. Tumor specimens of patients whose TIL were expanded in rIL-2 had significantly higher numbers per field (423 +/- 114 vs 154 +/- 20; P = 0.005) and proportions (90 +/- 3% vs 77 +/- 4%; P = 0.023) of infiltrating CD3+ cells, significantly higher numbers per field (115 +/- 44 vs 19 +/- 5; P = 0.003) and proportions (25 +/- 5% vs 11 +/- 2%; P = 0.017) of CD8+ cells and significantly higher numbers per field of CD4+ cells (318 +/- 101 vs 113 +/- 18; P = 0.025), in comparison to tumor specimens from patients whose TIL did not grow in vitro. Significant correlations were observed between the proportions of HLA class I-positive EOC tumor cells and the numbers of infiltrating LCA-positive cells (r = 0.67; P = 0.005) CD3+ cells (r = 0.70; P = 0.002), CD4+ cells (r = 0.69; P = 0.003), and CD8+ cells (r = 0.82; P = 0.001). The proportions of HLA class II-positive tumor cells correlated positively (r = 0.45; P = 0.049) only with the numbers of CD8+-infiltrating cells. In conclusion, we report here that HLA class I expression on EOC cells correlates with T-cell infiltration in vivo and T-cell expansion in vitro, in low concentrations of rIL-2.
本研究旨在确定卵巢肿瘤细胞上的HLA I类或II类表达以及上皮性卵巢癌（EOC）组织中的淋巴细胞浸润是否与在低浓度重组白细胞介素-2（rIL-2）条件下体外扩增肿瘤浸润淋巴细胞（TIL）的能力有关。使用识别HLA I类或HLA II类的构架决定簇或白细胞分化抗原（LCA、CD3、CD4和CD8）的单克隆抗体进行免疫组织化学分析。20份标本中的18份（90%）EOC冰冻切片显示至少5%的肿瘤细胞有HLA I类和HLA II类表达。从同一肿瘤标本的另一部分，17例患者中的7例在低浓度rIL-2（200 - 600 IU/ml）条件下从TIL培养出T细胞系。与TIL未能生长的肿瘤相比，用rIL-2体外扩增TIL的肿瘤中HLA I类阳性肿瘤细胞比例显著更高（73±10% 比 40±10%）（P = 0.036）。然而，两组之间HLA II类阳性肿瘤细胞比例没有差异。TIL在rIL-2中得以扩增的患者的肿瘤标本，与TIL在体外未生长的患者的肿瘤标本相比，每视野浸润的CD3 +细胞数量（423±114 比 154±20；P = 0.005）和比例（90±3% 比 77±4%；P = 0.023）显著更高，CD8 +细胞数量（115±44 比 19±5；P = 0.003）和比例（25±5% 比 11±2%；P = 0.017）显著更高，CD4 +细胞每视野数量（318±101 比 113±18；P = 0.025）也显著更高。观察到HLA I类阳性EOC肿瘤细胞比例与浸润的LCA阳性细胞数量（r = 0.67；P = 0.005）、CD3 +细胞数量（r = 0.70；P = 0.002）、CD4 +细胞数量（r = 0.69；P = 0.003）和CD8 +细胞数量（r = 0.82；P = 0.001）之间存在显著相关性。HLA II类阳性肿瘤细胞比例仅与CD8 +浸润细胞数量呈正相关（r = 0.45；P = 0.049）。总之，我们在此报告，EOC细胞上的HLA I类表达与体内T细胞浸润以及在低浓度rIL-2条件下体外T细胞扩增相关。
