Li Chunmei, Wang Pei, Dong Zhizhong, Cao Weihan, Su Yanjun, Zhang Jianming, Zhao Shuyan, Wang Zhiyuan, Lei Zi, Shi Li, Cheng Ruochuan, Liu Wen
State Key Laboratory for Conservation and Utilization of Bio-resources and School of Life Sciences, Yunnan University, Kunming, Yunnan, 650091, China.
Department of Radiation Oncology, Cancer Institute, The First Affiliated Hospital and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, China.
J Exp Clin Cancer Res. 2025 Mar 11;44(1):91. doi: 10.1186/s13046-025-03341-7.
Active surveillance (AS) offers a viable alternative to surgical intervention for the management of indolent papillary thyroid carcinoma (PTC), helping to minimize the incidence of unnecessary treatment. However, the broader adoption of AS is hindered by the need for more reliable diagnostic markers. This study aimed to identify the differences between indolent and progressive PTC and find new targets for biomarker development and therapeutic strategies.
We used single-cell RNA sequencing (scRNA-seq) to analyze cellular differences in 10 early-stage PTC tumors. Findings were validated in an additional 25 tumors using cell co-culture, migration assays, immunofluorescence staining, flow cytometry, and analysis of data from The Cancer Genome Atlas (TCGA).
Tumor-infiltrating B cells (TIL-B), particularly germinal center B cells (GC-B), were more abundant in indolent PTC. These cells suppressed thyroid cell proliferation in both indolent and progressive cases, though indolent PTC had a higher capacity to recruit peripheral B cells. In indolent cases, TIL-B cells showed increased proliferation and formed clusters within tertiary lymphoid structures (TLS). PTPRC-CD22 interactions were identified as potential drivers of TIL-B cell proliferation. Markers linked to GC-B cells, such as LMO2, were highlighted as potential diagnostic and prognostic indicators for indolent PTC.
This study provides insights into the cellular landscape of early-stage PTC, revealing distinct tumor and immune microenvironment features in indolent and progressive cases. These findings advance the understanding of indolent PTC biology and support the development of reliable diagnostic and prognostic biomarkers.
主动监测（AS）为惰性乳头状甲状腺癌（PTC）的治疗提供了一种可行的手术干预替代方案，有助于将不必要治疗的发生率降至最低。然而，更广泛地采用AS受到需要更可靠诊断标志物的阻碍。本研究旨在确定惰性和进展性PTC之间的差异，并寻找生物标志物开发和治疗策略的新靶点。
我们使用单细胞RNA测序（scRNA-seq）分析了10例早期PTC肿瘤的细胞差异。使用细胞共培养、迁移试验、免疫荧光染色、流式细胞术以及来自癌症基因组图谱（TCGA）的数据分析，在另外25个肿瘤中对研究结果进行了验证。
肿瘤浸润B细胞（TIL-B），尤其是生发中心B细胞（GC-B），在惰性PTC中更为丰富。这些细胞在惰性和进展性病例中均抑制甲状腺细胞增殖，尽管惰性PTC招募外周B细胞的能力更高。在惰性病例中，TIL-B细胞增殖增加，并在三级淋巴结构（TLS）内形成簇。PTPRC-CD22相互作用被确定为TIL-B细胞增殖的潜在驱动因素。与GC-B细胞相关的标志物，如LMO2，被强调为惰性PTC的潜在诊断和预后指标。
本研究提供了对早期PTC细胞格局的见解，揭示了惰性和进展性病例中不同的肿瘤和免疫微环境特征。这些发现增进了对惰性PTC生物学的理解，并支持开发可靠的诊断和预后生物标志物。
