Breast Center, The Second Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, China.
Department of Pathology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Front Immunol. 2022 Dec 13;13:1048503. doi: 10.3389/fimmu.2022.1048503. eCollection 2022.
INTRODUCTION: Immune checkpoint inhibitors (ICIs) have shown promising results for the treatment of multiple cancers. ICIs and related therapies may also be useful for the treatment of thyroid cancer (TC). In TC, Myc binding protein 2 (MYCBP2) is correlated with inflammatory cell infiltration and cancer prognosis. However, the relationship between MYCBP2 expression and ICI efficacy in TC patients is unclear. METHODS: We downloaded data from two TC cohorts, including transcriptomic data and clinical prognosis data. The Tumor Immune Dysfunction and Exclusion (TIDE) algorithm was used to predict the efficacy of ICIs in TC patients. MCPcounter, xCell, and quanTIseq were used to calculate immune cell infiltration scores. Gene set enrichment analysis (GSEA) and single sample GSEA (ssGSEA) were used to evaluate signaling pathway scores. Immunohistochemical (IHC) analysis and clinical follow up was used to identify the MYCBP2 protein expression status in patients and associated with clinical outcome. RESULTS: A higher proportion of MYCBP2-high TC patients were predicted ICI responders than MYCBP2-low patients. MYCBP2-high patients also had significantly increased infiltration of CD8+ T cells, cytotoxic lymphocytes (CTLs), B cells, natural killer (NK) cells and dendritic cells (DC)s. Compared with MYCBP2-low patients, MYCBP2-high patients had higher expression of genes associated with B cells, CD8+ T cells, macrophages, plasmacytoid dendritic cells (pDCs), antigen processing and presentation, inflammatory stimulation, and interferon (IFN) responses. GSEA and ssGSEA also showed that MYCBP2-high patients had significantly increased activity of inflammatory factors and signaling pathways associated with immune responses.In addiation, Patients in our local cohort with high MYCBP2 expression always had a better prognosis and greater sensitivity to therapy while compared to patients with low MYCBP2 expression after six months clinic follow up. CONCLUSIONS: In this study, we found that MYCBP2 may be a predictive biomarker for ICI efficacy in TC patients. High MYCBP2 expression was associated with significantly enriched immune cell infiltration. MYCBP2 may also be involved in the regulation of signaling pathways associated with anti-tumor immune responses or the production of inflammatory factors.
简介：免疫检查点抑制剂（ICIs）在治疗多种癌症方面显示出了可喜的结果。ICI 及其相关疗法也可能对甲状腺癌（TC）的治疗有用。在 TC 中，Myc 结合蛋白 2（MYCBP2）与炎症细胞浸润和癌症预后相关。然而，MYCBP2 表达与 TC 患者接受 ICI 治疗效果之间的关系尚不清楚。
方法：我们从两个 TC 队列中下载了数据，包括转录组数据和临床预后数据。使用肿瘤免疫功能障碍和排除（TIDE）算法预测 TC 患者接受 ICI 治疗的疗效。使用 MCPcounter、xCell 和 quanTIseq 计算免疫细胞浸润评分。基因集富集分析（GSEA）和单样本 GSEA（ssGSEA）用于评估信号通路评分。免疫组织化学（IHC）分析和临床随访用于确定患者中 MYCBP2 蛋白的表达状态及其与临床结果的关系。
结果：与 MYCBP2 低表达患者相比，更多的 MYCBP2 高表达 TC 患者被预测为 ICI 反应者。MYCBP2 高表达患者的 CD8+T 细胞、细胞毒性淋巴细胞（CTLs）、B 细胞、自然杀伤（NK）细胞和树突状细胞（DC）浸润也显著增加。与 MYCBP2 低表达患者相比，MYCBP2 高表达患者的 B 细胞、CD8+T 细胞、巨噬细胞、浆细胞样树突状细胞（pDCs）、抗原加工和呈递、炎症刺激和干扰素（IFN）反应相关基因的表达水平更高。GSEA 和 ssGSEA 还显示，MYCBP2 高表达患者的炎症因子和与免疫反应相关的信号通路活性显著增加。此外，在我们的本地队列中，与 MYCBP2 低表达患者相比，经过六个月的临床随访，表达高 MYCBP2 的患者始终具有更好的预后和对治疗的更高敏感性。
结论：在这项研究中，我们发现 MYCBP2 可能是 TC 患者接受 ICI 治疗效果的预测性生物标志物。高 MYCBP2 表达与显著丰富的免疫细胞浸润有关。MYCBP2 还可能参与调节与抗肿瘤免疫反应或炎症因子产生相关的信号通路。
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