Merogi A J, Marrogi A J, Ramesh R, Robinson W R, Fermin C D, Freeman S M
Department of Pathology, Tulane University Medical Center, New Orleans, LA 70112-2699, USA.
Hum Pathol. 1997 Mar;28(3):321-31. doi: 10.1016/s0046-8177(97)90131-3.
The host-tumor interaction may play an important role in determining tumor progress. Recent studies have shown that this interaction can be influenced by the release of soluble factors by tumor cells and tumor-infiltrating lymphocytes (TIL). The aim of our study is to characterize the nature of cytokines and growth factors and their relationship to the cellular infiltrates in 16 patients with ovarian cancer using reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry. Total RNA from 20 malignant and 10 benign specimens were used to assay for expression of 12 cytokines. Additionally, monoclonal antibodies (MAbs) were used to detect T cells, CD4+ helper and CD8+ cytotoxic/suppressor T-cell subtypes, B cells, and macrophages. Our results showed the expression of transforming growth factor-beta1 (TGF-beta1), interleukin-10 (IL-10), and granulocyte-macrophage colony-stimulating factor (GM-CSF) in 19, 17, and 10 malignant specimens, P < .001, .001, and .05, respectively. Other cytokines such as interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), TNF-beta/LT, IL-2, and IL-6 were expressed in a few cases, and IL-1alpha and IL-4 expression were not detected. The benign samples did not express IL-10, but GM-CSF, TGF-beta1, and IL-8 were expressed in one, one, and four specimens, respectively. Interestingly, in four cases in which samples from the primary and relapse tumors were available for analysis, the tumors in relapse showed a significant increase for TGF-beta1 (P < .05) and a decreased trend in IL-10 mRNA levels. The source of these factors was tumor cells as detected immunohistochemically. This combined alteration of TGF-beta1 and IL-10 was associated with a significant reduction in number of TIL in general, and CD8+ and macrophages in particular (P = .036 and .049, respectively). Our findings suggest the important role of certain soluble factors in the complex process of tumor progression. Furthermore, understanding the tumor-host relationship and the factors influencing the interaction may be helpful in developing effective and innovative treatment methods.
宿主-肿瘤相互作用可能在决定肿瘤进展过程中发挥重要作用。最近的研究表明，这种相互作用会受到肿瘤细胞和肿瘤浸润淋巴细胞（TIL）释放的可溶性因子的影响。我们研究的目的是利用逆转录聚合酶链反应（RT-PCR）和免疫组织化学方法，对16例卵巢癌患者体内细胞因子和生长因子的性质及其与细胞浸润的关系进行表征。从20个恶性标本和10个良性标本中提取的总RNA用于检测12种细胞因子的表达。此外，使用单克隆抗体（MAb）检测T细胞、CD4+辅助性T细胞和CD8+细胞毒性/抑制性T细胞亚型、B细胞及巨噬细胞。我们的结果显示，转化生长因子-β1（TGF-β1）、白细胞介素-10（IL-10）和粒细胞-巨噬细胞集落刺激因子（GM-CSF）在19个、17个和10个恶性标本中表达，P值分别<0.001、0.001和0.05。其他细胞因子如干扰素-γ（IFN-γ）、肿瘤坏死因子-α（TNF-α）、TNF-β/LT、IL-2和IL-6在少数病例中表达，未检测到IL-1α和IL-4的表达。良性样本未表达IL-10，但GM-CSF、TGF-β1和IL-8分别在1个、1个和4个标本中表达。有趣的是，在4例可获得原发肿瘤和复发肿瘤样本进行分析的病例中，复发肿瘤中TGF-β1显著增加（P<0.05），IL-10 mRNA水平呈下降趋势。免疫组织化学检测显示这些因子的来源是肿瘤细胞。TGF-β1和IL-10的这种联合改变总体上与TIL数量显著减少有关，尤其是CD8+细胞和巨噬细胞（P值分别为0.036和0.049）。我们的研究结果表明某些可溶性因子在肿瘤进展的复杂过程中发挥重要作用。此外，了解肿瘤-宿主关系以及影响这种相互作用的因素可能有助于开发有效且创新的治疗方法。
