Department of Pathology, Medical University-Pleven, 5800 Pleven, Bulgaria.
Department of Breast Surgery, Shterev Hospital, 1000 Sofia, Bulgaria.
Medicina (Kaunas). 2023 Apr 7;59(4):728. doi: 10.3390/medicina59040728.
The tumor microenvironment (TME) plays a major role in neoplastic development. Various types of cells can be found in the TME. These cells can be classified into two groups, immunosuppressive and immunostimulatory types, depending on the function they perform in the antitumor immune response (IR). By interacting both with each other and with tumor cells, different immune mechanisms are activated or inhibited, which can suppress or promote the development and progression of cervical cancer (CC). Our aim was to investigate some of the main components of the cellular immune response in TME-tumor-infiltrating cytotoxic T cells (Tc, CD8+) and tumor-associated macrophages (TAMs, CD68+)-in patients with CC. We analyzed 72 paraffin-embedded tumor tissues of patients diagnosed and treated at Medical University Pleven, Bulgaria. Patients were classified according to the 2018 FIGO (International Federation of Gynaecology and Obstetrics) classification. From each patient, we selected one histological slide with hematoxylin eosin staining. In a microscopic evaluation, CD8+ T lymphocytes and CD68+-positive macrophages were counted in the tumor and stroma of five randomly selected fields at ×40 magnification (HPF). We analyzed the relationship between intratumoral and stromal CD8 and CD68 expression and FIGO stage and N status. There was no significant association between the expression levels of intratumoral and stromal CD68+ cells in the different FIGO stages and according to the lymph nodes' involvement. For CD8+ cells, the association of stromal infiltration was also not found, but T intratumor infiltration was associated with a higher FIGO stage, despite the fact that the results did not reach significance ( = 0.063, Fisher test). Intratumoral CD8+ cells were significantly associated with positive N status, ( = 0.035). The separation of tumor-infiltrating cytotoxic T cells and tumor-associated macrophages into intratumoral and stromal is inconsequential. In our study, the level of infiltration of CD68+ cells in tumors and stromata was not significantly associated with tumor progression or lymph node involvement. The results were different for CD8+ cells, in which levels of infiltration were associated with lymph nodes' statuses. : The separate evaluation of CD68+ immune cells in the TME as intratumoral and stromal is not beneficial for defining prognoses, since the presence of these cells is not associated with the patient's stage. In our study, the presence of CD8+ cells was significantly associated with lymph node metastases. The prognostic value of the obtained results can be enriched with an additional study of the lymphocyte phenotype, including B and other subtypes of T lymphocytes, NK cells, as well as molecules involved in the immune response, such as HLA subtypes.
肿瘤微环境(TME)在肿瘤发生发展中起着重要作用。TME 中存在各种类型的细胞。这些细胞可以根据其在抗肿瘤免疫反应(IR)中的功能分为两类:免疫抑制型和免疫刺激型。不同的免疫机制通过相互作用以及与肿瘤细胞的相互作用被激活或抑制,这可能抑制或促进宫颈癌(CC)的发展和进展。我们的目的是研究 TME-肿瘤浸润细胞毒性 T 细胞(Tc,CD8+)和肿瘤相关巨噬细胞(TAMs,CD68+)中一些细胞免疫反应的主要成分在 CC 患者中的作用。我们分析了保加利亚普罗夫迪夫医科大学诊断和治疗的 72 例石蜡包埋肿瘤组织的患者。根据 2018 年 FIGO(国际妇产科联合会)分类对患者进行分类。从每位患者中,我们选择一张苏木精-伊红染色的组织学幻灯片。在显微镜评估中,在五个随机选择的视野中以 ×40 放大倍数(HPF)计数肿瘤和基质中 CD8+T 淋巴细胞和 CD68+阳性巨噬细胞的数量。我们分析了肿瘤内和基质中 CD8 和 CD68 表达与 FIGO 分期和 N 状态之间的关系。在不同的 FIGO 分期和根据淋巴结受累情况,肿瘤内和基质中 CD68+细胞的表达水平之间没有显著的相关性。对于 CD8+细胞,也没有发现基质浸润的相关性,但肿瘤内浸润与更高的 FIGO 分期相关,尽管结果没有达到显著性(=0.063,Fisher 检验)。肿瘤内 CD8+细胞与阳性 N 状态显著相关(=0.035)。将肿瘤浸润细胞毒性 T 细胞和肿瘤相关巨噬细胞分离为肿瘤内和基质内是没有意义的。在我们的研究中,肿瘤和基质中 CD68+细胞浸润的水平与肿瘤进展或淋巴结受累没有显著相关性。对于 CD8+细胞,其浸润水平与淋巴结状态相关。结果不同,CD8+细胞浸润水平与淋巴结状态相关。结论:将 TME 中的 CD68+免疫细胞作为肿瘤内和基质内分别评估对于定义预后没有益处,因为这些细胞的存在与患者的分期无关。在我们的研究中,CD8+细胞的存在与淋巴结转移显著相关。获得的结果的预后价值可以通过进一步研究淋巴细胞表型(包括 B 和其他 T 淋巴细胞亚型、NK 细胞以及参与免疫反应的分子,如 HLA 亚型)来丰富。