Department of Breast and Thyroid Surgery, Kitasato University Hospital, Sagamihara, Kanagawa, Japan.
Department of Breast and Thyroid Surgery, Kitasato University Hospital, Sagamihara, Kanagawa, Japan.
J Surg Res. 2024 Nov;303:532-544. doi: 10.1016/j.jss.2024.09.035. Epub 2024 Oct 19.
Skewed immune response plays a pivotal role in tumor progression. Systemic inflammatory responses represented by combined peripheral leukocyte fractions are prognostic predictors of multiple cancers, including thyroid cancer. We previously reported the prognostic significance of lymphocyte-to-monocyte ratio (LMR) in curatively resected papillary thyroid cancer (PTC). Therefore, this study aimed to analyze immune cell profiles in the tumor microenvironment and their association with LMR in curatively resected PTC.
The immune cell profiles of primary tumors in 162 patients with curatively resected PTC were analyzed clinicopathologically. Immunohistochemistry of tumor-associated macrophages (TAMs), myeloid-derived suppressor cells, and lymphocytes was performed using CD163, CD33, and CD3 antibodies, respectively. Prognostic analysis and correlation assays were performed using the immunocyte profiles. The gene expression of tumor-derived chemokines was assessed using a The Cancer Genome Atlas database.
Patients with a higher density of CD163 TAMs exhibited a significantly worse prognosis than their counterparts (10-y recurrence-free survival: 80.9% versus 91.2%, P = 0.011). Multivariate prognostic analyses revealed that high CD163 cell density (P = 0.011), low preoperative LMR (P = 0.003), pN1b (P = 0.005), and high thyroglobulin level (P = 0.038) were independent predictors of recurrence. High CD163 cell density had a prognostic impact on stage II and III PTC. Interestingly, high CD163 cell density correlated with low LMR and high monocyte fraction in peripheral blood. Indeed, the expression of TAM-inducible, tumor-derived chemokines is increased in the The Cancer Genome Atlas database.
A high density of infiltrated CD163 TAMs predicts recurrence in correlation with low LMR and circulating monocyte accumulation. Thus, TAMs should be considered when assessing advanced PTC.
免疫反应偏倚在肿瘤进展中起着关键作用。外周白细胞分数综合代表的全身炎症反应是多种癌症（包括甲状腺癌）的预后预测指标。我们之前报道了淋巴细胞与单核细胞比值（LMR）在可治愈性切除的甲状腺乳头状癌（PTC）中的预后意义。因此，本研究旨在分析可治愈性切除的 PTC 肿瘤微环境中的免疫细胞谱及其与 LMR 的关系。
分析了 162 例可治愈性切除的 PTC 患者的原发性肿瘤的免疫细胞谱。使用 CD163、CD33 和 CD3 抗体分别对肿瘤相关巨噬细胞（TAMs）、髓系来源的抑制细胞和淋巴细胞进行免疫组织化学染色。使用免疫细胞谱进行预后分析和相关性分析。使用癌症基因组图谱数据库评估肿瘤衍生趋化因子的基因表达。
CD163 TAMs 密度较高的患者预后明显较差（10 年无复发生存率：80.9%对 91.2%，P=0.011）。多因素预后分析显示，高 CD163 细胞密度（P=0.011）、术前低 LMR（P=0.003）、pN1b（P=0.005）和高甲状腺球蛋白水平（P=0.038）是复发的独立预测因素。高 CD163 细胞密度对 II 期和 III 期 PTC 有预后影响。有趣的是，高 CD163 细胞密度与外周血中低 LMR 和高单核细胞分数相关。事实上，在癌症基因组图谱数据库中，TAM 诱导的肿瘤衍生趋化因子的表达增加。
浸润性 CD163 TAMs 密度高与低 LMR 和循环单核细胞积累相关，预示着复发。因此，在评估晚期 PTC 时应考虑 TAMs。
