Shigematsu Yasuyuki, Kanda Hiroaki, Takahashi Yu, Takeuchi Kengo, Inamura Kentaro
Department of Pathology, Cancer Institute Hospital, Japanese Foundation for Cancer Research (JFCR), 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan.
Division of Pathology, Cancer Institute, JFCR, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan.
Virchows Arch. 2024 Oct 12. doi: 10.1007/s00428-024-03939-w.
In hepatocellular carcinoma (HCC), CD147 expression contributes to tumor malignancy; however, its relationship with the tumor-immune microenvironment (TIME) remains unclear. This study aimed to elucidate the clinicopathological characteristics associated with CD147 expression in HCC and investigate its association with the TIME, specifically its association with tumor-infiltrating lymphocytes (TILs) and oncostatin M (OSM). Using 397 HCC specimens from patients undergoing curative-intent resection, we assessed CD147 expression in tumor cells and quantified OSM-positive cells and various TILs (CD8, CD4, FOXP3, and CD20 cells) in the TIME. Using tissue microarrays, these assessments were performed through immunohistochemical analysis. We investigated the associations between CD147 expression status, the density of OSM-positive cells, and the densities of various TILs. High CD147 expression, found in 332 specimens (83.6%), was associated with advanced clinical stage (P = 0.029), fibrosis (P = 0.036), and higher densities of FOXP3 cells (P = 0.0039), CD4 cells (P = 0.0012), and OSM-positive cells (P = 0.0017). In CD147-high tumors, OSM-positive cell density was associated with all assessed TIL subsets (CD8, CD4, FOXP3, and CD20 cells; all Ps < 0.001), whereas in CD147-low tumors, OSM-positive cell density was associated only with FOXP3 cells (P = 0.0004). In HCC, CD147 expression is associated with an immunosuppressive TIME, characterized by increased FOXP3 regulatory T cells and a correlation with OSM-positive cells. These results elucidate the potential mechanisms through which CD147 facilitates tumor-immune evasion, suggesting the CD147 - OSM axis as a promising target for therapeutic intervention in HCC.
在肝细胞癌(HCC)中,CD147表达促进肿瘤恶性进展;然而,其与肿瘤免疫微环境(TIME)的关系仍不清楚。本研究旨在阐明与HCC中CD147表达相关的临床病理特征,并研究其与TIME的关联,特别是其与肿瘤浸润淋巴细胞(TILs)和抑瘤素M(OSM)的关联。我们使用来自接受根治性切除患者的397份HCC标本,评估肿瘤细胞中CD147的表达,并对TIME中的OSM阳性细胞和各种TILs(CD8、CD4、FOXP3和CD20细胞)进行定量。使用组织微阵列,通过免疫组织化学分析进行这些评估。我们研究了CD147表达状态、OSM阳性细胞密度和各种TILs密度之间的关联。在332份标本(83.6%)中发现的高CD147表达与晚期临床分期(P = 0.029)、纤维化(P = 0.036)以及FOXP3细胞(P = 0.0039)、CD4细胞(P = 0.0012)和OSM阳性细胞(P = 0.0017)的较高密度相关。在CD147高表达的肿瘤中,OSM阳性细胞密度与所有评估的TIL亚群(CD8、CD4、FOXP3和CD20细胞;所有P < 0.001)相关,而在CD147低表达的肿瘤中,OSM阳性细胞密度仅与FOXP3细胞相关(P = 0.0004)。在HCC中,CD147表达与免疫抑制性TIME相关,其特征是FOXP3调节性T细胞增加且与OSM阳性细胞相关。这些结果阐明了CD147促进肿瘤免疫逃逸的潜在机制,表明CD147-OSM轴是HCC治疗干预的一个有前景的靶点。