Elevation of the Prognostic Factor Plasma Fibrinogen Reflects the Immunosuppressive Tumor Microenvironment in Esophageal Squamous Cell Carcinoma
Elevation of the Prognostic Factor Plasma Fibrinogen Reflects the Immunosuppressive Tumor Microenvironment in Esophageal Squamous Cell Carcinoma
复制标题
DOI：
10.1245/s10434-022-11974-7
复制
发表时间：
2022-06-07
影响因子：
3.7
通讯作者：
Kitagawa, Yuko
中科院分区：
文献类型：
--
作者：
Hoshino, Shota;Matsuda, Satoru;Kitagawa, Yuko
导言。尽管已有报道指出血浆纤维蛋白原(FNG)水平作为ESCC预后指标的临床意义，但其潜在机制仍不清楚。本研究旨在验证血浆FNG水平对食管鳞癌患者预后的影响，并阐明其与原发肿瘤的关系。对2000年至2019年间接受食道切除术的ESCC患者进行了FNG对预后的影响评估。对手术前活检的原发ESCC部位进行RNA测序，然后使用免疫图进行免疫图谱分析。通过肿瘤相关巨噬细胞(TAMs)的免疫组织化学染色和尼伏拉单抗的临床反应来评估这些特征。多因素分析表明，FNG是ESCC的一个重要预后因素。免疫图谱显示高FNG组肿瘤细胞处于免疫抑制状态，标记CD163和CD204免疫组化染色显示高FNG组TAM数显著高于低FNG组。转移性ESCC患者的免疫抑制特征在临床上得到了验证；那些FNG水平升高的患者对尼伏莫的反应较差。这项研究在扩展的ESCC队列中成功验证了血浆FNG水平对预后的影响。因此，我们的发现表明，血浆FNG的增加反映了免疫抑制的肿瘤微环境，这种微环境促进了肿瘤的进展，并对nivolumab的反应较差。
Introduction. Despite previous reports on the clinical significance of plasma fibrinogen (FNG) levels as a prognostic indicator of ESCC, its underlying mechanism remains unclear. This study aimed to validate the prognostic impact of plasma FNG levels and clarify its relationship with primary tumors in patients with esophageal squamous cell carcinoma (ESCC).Methods. The prognostic impact of FNG was evaluated in patients with ESCC who underwent esophagectomy between 2000 and 2019. The RNA sequencing of the primary ESCC site, which was from pre-operative biopsy, was performed, followed by immune profile characterization using an immunogram. Those profiles were assessed via the immunohistochemical staining of tumor-associated macrophages (TAMs) and clinical response to nivolumab.Results. Multivariate analysis identified FNG as a significant prognostic factor in ESCC. The immunogram suggested an immunosuppressive tumor environment in the high-FNG group Immunostaining with the TAM markers CD163 and CD204, revealed that the high-FNG group had significantly higher number of TAMs compared with the low-FNG group. The immunosuppressive characteristics were clinically validated in patients with metastatic ESCC; those who had elevated FNG levels showed poor response to nivolumab.Conclusion. This study successfully validated the prognostic impact of plasma FNG levels in an expanded cohort with ESCC. Accordingly, our findings showed that increased plasma FNG reflects an immunosuppressive tumor microenvironment that facilitates tumor progression and poor responses to nivolumab.