为肝细胞癌武装 GPC3 CAR-T 细胞:多少才足够,下一步是什么?
Armouring GPC3 CAR T cells for hepatocellular carcinoma: how much is enough and what comes next?
英文原题:Relationships between tumor CD147 expression, tumor-infiltrating lymphocytes, and oncostatin M in hepatocellular carcinoma.
Relationships between tumor CD147 expression, tumor-infiltrating lymphocytes, and oncostatin M in hepatocellular carcinoma.
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在 332 份标本(83.6%)中发现的高 CD147 表达与较晚的临床分期(P = 0.029)、纤维化(P = 0.036)以及更高的 FOXP3⁺ 细胞(P = 0.0039)、CD4⁺ 细胞(P = 0.0012)和 OSM 阳性细胞(P = 0.0017)密度相关。
肝细胞癌(HCC)中 CD147 表达会促进肿瘤恶性进展,但其与肿瘤免疫微环境(TIME)的关系仍不明确。本研究旨在阐明 HCC 中与 CD147 表达相关的临床病理特征,并研究其与 TIME 的关联,特别是与TIL(肿瘤浸润淋巴细胞)和抑瘤素 M(OSM)的关系。研究评估了 397 份接受根治意图切除患者的 HCC 标本中肿瘤细胞的 CD147 表达,并定量分析 TIME 中 OSM 阳性细胞及多种 TIL(CD8+、CD4+、FOXP3+ 和 CD20+ 细胞)。这些评估通过组织芯片免疫组织化学分析完成。研究分析了 CD147 表达状态与 OSM 阳性细胞密度及各类 TIL 密度之间的关联。332 份标本(83.6%)CD147 高表达;高表达与临床分期较晚(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)密度较高相关。在 CD147 高表达肿瘤中,OSM 阳性细胞密度与所评估的所有 TIL 亚群(CD8+、CD4+、FOXP3+ 和 CD20+ 细胞)均相关(所有 P < 0.001);而在 CD147 低表达肿瘤中,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,其特征为 FOXP3+ 调节性 T 细胞增加,并与 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,提示 CD147–OSM 轴有望成为 HCC 治疗干预的靶点。
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.
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