宫颈癌吞噬细胞和免疫调节标志物的综合分析揭示了潜在的预后相关性。
Integrated Analysis of Phagocytic and Immunomodulatory Markers in Cervical Cancer Reveals Constellations of Potential Prognostic Relevance.
发表日期:2024 Aug 22
作者:
Angel Yordanov, Polina Damyanova, Mariela Vasileva-Slaveva, Ihsan Hasan, Stoyan Kostov, Velizar Shivarov
来源:
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
摘要:
尽管疫苗接种、筛查和治疗有所改善,但宫颈癌 (CC) 仍然是全球范围内的一个主要医疗保健问题。肿瘤微环境(TME)在癌症发展中发挥着重要且有争议的作用,肿瘤逃避免疫监视的机制仍不清楚。我们的目的是研究具有不同组织学变异的 CC、肿瘤特征和负荷的患者中 CD68 和 CD47 的表达。这是一项回顾性队列研究,对 2014 年至 2021 年间在保加利亚普列文医科大学诊断为 CC 的 191 名患者的石蜡包埋肿瘤组织进行。获得用于免疫组织化学(IHC)评估的载玻片,并使用三点评分量表对瘤内(IT)和基质(ST)巨噬细胞(CD68细胞)中CD68的表达进行评分。 CD47 表达报告为 H 分数。所有统计分析均使用 Windows 版 R v. 4.3.1 进行。肿瘤中 CD68-IT 细胞的浸润取决于组织学类型和 CD47 的表达。早期患者中 CD47 H 评分水平较高的频率明显更高。 CD68-ST 细胞浸润水平较高与预后较差相关,CD68-IT 细胞浸润与肿瘤疾病死亡风险降低相关。 TME是一个复杂的生态系统,在肿瘤的生长和发展中发挥着重要作用。巨噬细胞是先天免疫的主要组成部分,当与肿瘤过程相关时,被定义为 TAM。肿瘤细胞试图通过三种方式逃避免疫监视,其中之一是通过肿瘤细胞表面的 T 淋巴细胞及其配体过度表达阴性辅助受体来降低免疫原性。其中一种机制是肿瘤细胞中 CD47 的表达,它向巨噬细胞发出“不要吃我”的信号,从而阻止吞噬作用。据我们所知,这是第一项尝试建立 CD47 和 CD68 表达水平与 CC 的一些临床病理特征之间关系的研究。我们发现,与 CD68 浸润水平相关的唯一临床病理学特征是肿瘤的组织学变异,并且仅在鳞状细胞癌中观察到 CD68-IT 高水平。高水平的CD47表达在FIGO I阶段中在pT1B中比pT2A中更常见,在FIGO I阶段中pT2B比在FIGO II和III阶段中更常见。在肿瘤细胞高表达 CD47 的患者中,大量 CD68-IT 细胞浸润更为常见。高水平的CD68-ST细胞浸润与较差的预后相关,高水平的CD68-ST细胞浸润与较低的癌症死亡风险相关。
Despite improvements in vaccination, screening, and treatment, cervical cancer (CC) remains a major healthcare problem on a global scale. The tumor microenvironment (TME) plays an important and controversial role in cancer development, and the mechanism of the tumor's escape from immunological surveillance is still not clearly defined. We aim to investigate the expression of CD68 and CD47 in patients with different histological variants of CC, tumor characteristics, and burden. This is a retrospective cohort study performed on paraffin-embedded tumor tissues from 191 patients diagnosed with CC between 2014 and 2021 at the Medical University Pleven, Bulgaria. Slides for immunohistochemical (IHC) evaluation were obtained, and the expression of CD68 was scored in intratumoral (IT) and stromal (ST) macrophages (CD68+cells) using a three-point scoring scale. The CD47 expression was reported as an H-score. All statistical analyses were performed using R v. 4.3.1 for Windows. Infiltration by CD68-IT cells in the tumor depended on histological type and the expression of CD47. Higher levels of the CD47 H-score were significantly more frequent among patients in the early stage. Higher levels of infiltration by CD68-ST cells were associated with worse prognosis, and the infiltration of CD68-IT cells was associated with reduced risk of death from neoplastic disease. TME is a complex ecosystem that has a major role in the growth and development of tumors. Macrophages are a major component of innate immunity and, when associated with a tumor process, are defined as TAM. Tumor cells try to escape immunological surveillance in three ways, and one of them is reducing immunogenicity by the overexpression of negative coreceptors by T-lymphocytes and their ligands on the surface of tumor cells. One such mechanism is the expression of CD47 in tumor cells, which sends a "don't eat me" signal to the macrophages and, thus, prevents phagocytosis. To our knowledge, this is the first study that has tried to establish the relationship between the CD47 and CD68 expression levels and some clinicopathologic features in CC. We found that the only clinicopathological feature implicating the level of CD68 infiltration was the histological variant of the tumor, and only for CD68-IT-high levels were these observed in SCC. High levels of CD47 expression were seen more frequently in pT1B than pT2A and pT2B in the FIGO I stage than in the FIGO II and III stages. Infiltration by large numbers of CD68-IT cells was much more common among patients with a high expression of CD47 in tumor cells. A high level of infiltration by CD68-ST cells was associated with a worse prognosis, and a high level of infiltration by CD68-ST cells was associated with a lower risk of death from cancer.