Melichar B, Savary C, Kudelka A P, Verschraegen C, Kavanagh J J, Edwards C L, Platsoucas C D, Freedman R S
Department of Gynecologic Oncology, The University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
Clin Cancer Res. 1998 Mar;4(3):799-809.
The characteristics of antigen-presenting cells in carcinomas that involve the abdominopelvic cavity are unknown. Dendritic cells, a population of antigen-presenting cells, have been identified as lineage-negative human leukocyte antigen (HLA)-DR+ cells by two-color flow cytometry. We used this criterion to study the putative dendritic cells in ascites from 25 patients with peritoneal carcinomatosis. The mean proportion +/- SD of lineage-negative HLA-DR+ cells in ascites was 3.1 +/- 4.6% (range, 0.05-17.3%). Most lineage-negative HLA-DR+ cells expressed CD45RA or CD4 antigens. Dendritic cells had low proportions of CD80, CD11c, CD45RO, and CD58, suggesting that they were of low maturity. The proportion of lineage-negative HLA-DR+ cells in ascites of seven patients was significantly higher than the proportion in peripheral blood from the identical patients (4.5 +/- 5.7 versus 0.5 +/- 0.4; P < 0.05). In paired specimens of ascites and peripheral blood, the proportion of lineage-negative HLA-DR+ cells that coexpressed CD86 or CD58 was significantly lower in ascites than in peripheral blood, whereas a higher proportion of lineage-negative HLA-DR+ cells in ascites expressed CD4. Relative fluorescence intensity of HLA-DR+ was also lower in dendritic cells from ascites and blood from patients with carcinomatosis than it was in blood from normal donors. As an indicator of macrophage activation, the concentration of neopterin in ascitic fluid correlated negatively with the numbers of lineage-negative HLA-DR+ cells in ascites (Spearman correlation coefficient, -0.44; P = 0.05) correlated positively with the concentration of interleukin 10 in ascitic fluid (Spearman correlation coefficient, -0.40; P = 0.05). IFN-gamma and tumor necrosis factor alpha were also not detected. These findings suggest that certain factors associated with the tumor microenvironment might influence the number of these dendritic cells and their expression of function-associated markers.
累及腹腔的癌组织中抗原呈递细胞的特征尚不清楚。树突状细胞作为抗原呈递细胞的一种，已通过双色流式细胞术被鉴定为谱系阴性的人类白细胞抗原（HLA）-DR+细胞。我们采用这一标准研究了25例腹膜癌患者腹水中的假定树突状细胞。腹水中谱系阴性HLA-DR+细胞的平均比例±标准差为3.1±4.6%（范围为0.05-17.3%）。大多数谱系阴性HLA-DR+细胞表达CD45RA或CD4抗原。树突状细胞的CD80、CD11c、CD45RO和CD58比例较低，表明它们成熟度较低。7例患者腹水中谱系阴性HLA-DR+细胞的比例显著高于同一患者外周血中的比例（4.5±5.7对0.5±0.4；P<0.05）。在腹水和外周血的配对样本中，共表达CD86或CD58的谱系阴性HLA-DR+细胞在腹水中的比例显著低于外周血，而腹水中表达CD4的谱系阴性HLA-DR+细胞比例更高。癌患者腹水和血液中的树突状细胞中HLA-DR+的相对荧光强度也低于正常供体血液中的。作为巨噬细胞活化的指标，腹水中新蝶呤的浓度与腹水中谱系阴性HLA-DR+细胞的数量呈负相关（斯皮尔曼相关系数，-0.44；P=0.05），与腹水中白细胞介素10的浓度呈正相关（斯皮尔曼相关系数，-0.40；P=0.05）。也未检测到干扰素-γ和肿瘤坏死因子α。这些发现表明，与肿瘤微环境相关的某些因素可能会影响这些树突状细胞的数量及其功能相关标志物的表达。
