Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center and James Cancer Hospital, Columbus, Ohio.
Department of Pathology, The Ohio State University Wexner Medical Center, Columbus, Ohio.
J Surg Res. 2020 Dec;256:458-467. doi: 10.1016/j.jss.2020.07.032. Epub 2020 Aug 12.
Despite the advances in treatment of differentiated thyroid cancer (DTC), predicting prognosis remains a challenge. Immune cells in the tumor microenvironment may provide an insight to predicting recurrence. Therefore, the objective of this study was to investigate the association of tumor-associated macrophages (TAMs) and tumor-associated neutrophils (TANs) with recurrence in DTC and to identify serum cytokines that correlate with the presence of these immune cells in the tumor.
Forty-two DTC tissues from our institutional neoplasia repository were stained for immunohistochemistry markers for TAMs and TANs. In addition, cytokine levels were analyzed from these patients from preoperative blood samples. TAM and TAN staining were compared with clinical data and serum cytokine levels.
Neither TAM nor TAN scores alone correlated with tumor size, the presence of lymph node metastases, multifocal tumors, lymphovascular or capsular invasion, or the presence of BRAFV600E mutation (all P > 0.05). There was no association with recurrence-free survival (RFS) in TAN density (mean RFS, 169.1 versus 148.1 mo, P = 0.23) or TAM density alone (mean RFS, 121.3 versus 205.2 mo, P = 0.54). However, when scoring from both markers were combined, patients with high TAM density and TAN negative scores had significantly lower RFS (mean RFS, 50.7 versus 187.3 mo, P = 0.04) compared with the remaining cohort. Patients with high TAM/negative TAN tumors had significantly lower serum levels of interleukin 12p70, interleukin 8, tumor necrosis factor alpha, and tumor necrosis factor beta.
In DTCs, high density of TAMs in the absence of TANs is associated with worse outcome. Assessment of multiple immune cell types and serum cytokines may predict outcomes in DTC.
尽管分化型甲状腺癌(DTC)的治疗取得了进展,但预测预后仍然是一个挑战。肿瘤微环境中的免疫细胞可能为预测复发提供线索。因此,本研究的目的是探讨肿瘤相关巨噬细胞(TAMs)和肿瘤相关中性粒细胞(TANs)与 DTC 复发的关系,并确定与肿瘤中这些免疫细胞存在相关的血清细胞因子。
从我们机构肿瘤库中选择 42 例 DTC 组织进行 TAMs 和 TANs 的免疫组织化学标志物染色。此外,还分析了这些患者术前血样中的细胞因子水平。比较 TAM 和 TAN 染色与临床资料和血清细胞因子水平的关系。
TAM 或 TAN 评分均与肿瘤大小、淋巴结转移、多灶性肿瘤、血管淋巴管或包膜侵犯以及 BRAFV600E 突变的存在无关(均 P>0.05)。TAN 密度与无复发生存率(RFS)无相关性(平均 RFS,169.1 与 148.1 个月,P=0.23),TAM 密度也无相关性(平均 RFS,121.3 与 205.2 个月,P=0.54)。然而,当两种标志物联合评分时,TAM 密度高且 TAN 阴性评分的患者 RFS 显著降低(平均 RFS,50.7 与 187.3 个月,P=0.04),与其余队列相比。TAM/阴性 TAN 肿瘤患者的血清白细胞介素 12p70、白细胞介素 8、肿瘤坏死因子-α 和肿瘤坏死因子-β 水平显著降低。
在 DTC 中,TAMs 密度高而 TANs 密度低与预后不良相关。评估多种免疫细胞类型和血清细胞因子可能有助于预测 DTC 的预后。