Kim Wonkyung, Oh Ji-Hye, Park Chae Won, Kim Hyori, Kang Young Gwang, Oh Da Eun, Lee Hee Jin, Kim Ji Hun, Sung Chang Ohk
Department of Medical Science, Brain Korea 21 Project, Asan Medical Institute of Convergence Science and Technology, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea.
Cancer Immunol Immunother. 2025 May 13;74(7):201. doi: 10.1007/s00262-025-04045-9.
Although the clinical significance of plasma cells within tumors has been recognized, studies on the development of plasma cells and the characteristics of the antibodies they secrete within the tumor microenvironment remain limited. We investigated the properties of plasma cells within cancer tissues using single-cell RNA and single cell B cell receptor sequencing. We characterized plasma cells exhibiting clonal expansion and synthesized the antibodies produced by these cells, confirming the clinical relevance of immunoglobulin H (IGH) isotypes. Plasma cells comprised approximately 5% of the total immune cell population within the tumor; clonal expansion was more prevalent in plasma cells than in B cells. Among plasma cells, the most frequent immunoglobulin isotype was IGHG1 and IGKC. We synthesized six recombinant antibodies, including those from the largest clonal plasma cells. Two antibodies that formed clones showed membranous staining in cancer cells. The cancer cells that metastasized to the lymph node showed a loss of expression as observed by immunohistochemistry. Analysis of bulk RNA sequencing data from 1078 patients with breast cancer revealed that tumor-infiltrating plasma cells expressing IGHG1 were associated with favorable prognoses. These tumors exhibited increased B cell receptor diversity, immunogenic mutation, and intratumoral heterogeneity. This study suggests the potential for discovering cancer-associated antibodies derived from intratumoral plasma cells.
尽管肿瘤内浆细胞的临床意义已得到认可，但关于浆细胞的发育以及它们在肿瘤微环境中分泌的抗体特性的研究仍然有限。我们使用单细胞RNA和单细胞B细胞受体测序研究了癌组织内浆细胞的特性。我们对表现出克隆扩增的浆细胞进行了表征，并合成了这些细胞产生的抗体，证实了免疫球蛋白H（IGH）同种型的临床相关性。浆细胞约占肿瘤内总免疫细胞群体的5%；克隆扩增在浆细胞中比在B细胞中更普遍。在浆细胞中，最常见的免疫球蛋白同种型是IGHG1和IGKC。我们合成了六种重组抗体，包括来自最大克隆浆细胞的抗体。两种形成克隆的抗体在癌细胞中显示出膜染色。通过免疫组织化学观察，转移至淋巴结的癌细胞显示出表达缺失。对1078例乳腺癌患者的批量RNA测序数据进行分析发现，表达IGHG1的肿瘤浸润浆细胞与良好预后相关。这些肿瘤表现出B细胞受体多样性增加、免疫原性突变和肿瘤内异质性。这项研究表明了发现源自肿瘤内浆细胞的癌症相关抗体的潜力。
