CD163+肿瘤相关巨噬细胞招募可预测甲状腺乳头状癌复发

IF 1.8 3区医学 Q2 SURGERY

Journal of Surgical Research Pub Date : 2024-10-19 DOI:10.1016/j.jss.2024.09.035

Hiroshi Katoh MD, PhD, FACS , Riku Okamoto MD , Mitsuo Yokota MD, PhD , Kanako Naito MD , Mariko Kikuchi MD, PhD , Takaaki Tokito MD , Takafumi Sangai MD, PhD , Keishi Yamashita MD, PhD, FACS

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引用次数: 0

摘要

简介免疫反应失衡在肿瘤进展中起着关键作用。以外周血白细胞组合分数为代表的全身炎症反应是包括甲状腺癌在内的多种癌症的预后预测指标。我们曾报道过淋巴细胞与单核细胞比值（LMR）在治愈性切除的甲状腺乳头状癌（PTC）中的预后意义。因此，本研究旨在分析肿瘤微环境中的免疫细胞图谱及其与治愈切除的PTC淋巴细胞比值的关系：对162例治愈切除的PTC患者原发肿瘤的免疫细胞谱进行临床病理分析。分别使用 CD163、CD33 和 CD3 抗体对肿瘤相关巨噬细胞（TAMs）、髓源抑制细胞和淋巴细胞进行免疫组化。利用免疫细胞图谱进行了预后分析和相关性测定。使用癌症基因组图谱数据库评估了肿瘤衍生趋化因子的基因表达：结果：CD163+ TAMs密度较高的患者的预后明显差于同类患者（10年无复发生存率：80.9%对91.2%，P = 0.011）。多变量预后分析显示，CD163+细胞密度高（P = 0.011）、术前LMR低（P = 0.003）、pN1b（P = 0.005）和甲状腺球蛋白水平高（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的预后有影响。有趣的是，CD163+细胞密度高与低LMR和外周血中单核细胞比例高相关。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量有所增加：结论：高密度浸润的 CD163+ TAM 与低 LMR 和循环单核细胞聚集相关，可预测复发。因此，在评估晚期 PTC 时应考虑 TAMs。

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CD163+ Tumor-Associated Macrophage Recruitment Predicts Papillary Thyroid Cancer Recurrence

Introduction

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.

Materials and methods

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.

Results

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.

Conclusions

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.

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来源期刊

Journal of Surgical Research 医学-外科

CiteScore

3.90

自引率

4.50%

发文量

627

审稿时长

138 days

期刊介绍： The Journal of Surgical Research: Clinical and Laboratory Investigation publishes original articles concerned with clinical and laboratory investigations relevant to surgical practice and teaching. The journal emphasizes reports of clinical investigations or fundamental research bearing directly on surgical management that will be of general interest to a broad range of surgeons and surgical researchers. The articles presented need not have been the products of surgeons or of surgical laboratories. The Journal of Surgical Research also features review articles and special articles relating to educational, research, or social issues of interest to the academic surgical community.