Department of Oncology, Affiliated Sixth People's Hospital, Shanghai Jiaotong University, Shanghai, China.
Department of Radiotherapy, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, Fujian, China.
Cell Biol Toxicol. 2023 Jun;39(3):1169-1180. doi: 10.1007/s10565-021-09672-3. Epub 2021 Nov 19.
With the advent of immune checkpoint inhibitors (ICIs) therapies, a major breakthrough has been made in cancer treatment. However, instead of good results, some patients experienced a deterioration of their disease. This unexpected result is termed as hyper-progressive disease (HPD). The biology of HPD is currently not fully understood.
Isolation of CD3 cells from peripheral blood mononuclear cells (PBMC) in healthy control, tumor patients receiving immunotherapy with or without immunotherapy-induced HPD, then conducted single-cell RNA sequencing (scRNA-seq).
By analyzing scRNA-seq data, we identified 15 cell clusters. We observed developed-exhausted CD4 T cells and regulatory T cells (Tregs) increasingly enriched in HPD group. Meanwhile, some effector T cells were decreased in HPD. The imbalance potentially contributes to the occurrence of HPD and poor clinical prognosis. In addition, we analyzed ligand-receptor interactions between subsets. The ligand-receptor interaction "CD74-MIF" was absent in HPD. However, in vitro experiment, we found that CD74 regulated effector function of effector CD8 T cells. Overall, the article provides a primary study of immune profile in HPD.
随着免疫检查点抑制剂（ICIs）疗法的出现，癌症治疗取得了重大突破。然而，一些患者的病情却出现了恶化，而非预期的治疗效果，这种情况被称为超进展性疾病（HPD）。目前，HPD 的生物学机制尚未完全阐明。
从健康对照者、接受免疫治疗和免疫治疗诱导的 HPD 的肿瘤患者的外周血单个核细胞（PBMC）中分离 CD3 细胞，然后进行单细胞 RNA 测序（scRNA-seq）。
通过分析 scRNA-seq 数据，我们鉴定出 15 个细胞簇。我们观察到在 HPD 组中，耗竭的 CD4 T 细胞和调节性 T 细胞（Tregs）逐渐富集。同时，一些效应 T 细胞在 HPD 中减少。这种失衡可能导致 HPD 的发生和不良的临床预后。此外，我们分析了亚群之间的配体-受体相互作用。在 HPD 中，配体-受体相互作用“CD74-MIF”缺失。然而，在体外实验中，我们发现 CD74 调节效应 CD8 T 细胞的效应功能。总体而言，本文对 HPD 中的免疫特征进行了初步研究。
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