Si Stephanie J, Wertheim Gerald B, Barrett David M
Children's Hospital of Philadelphia, Division of Oncology and Center for Childhood Cancer Research, Philadelphia, PA, United States.
Children's Hospital of Philadelphia, Department of Pathology and Laboratory Medicine, Philadelphia, PA, United States.
J Cancer Immunol (Wilmington). 2021;3(3):163-176. doi: 10.33696/cancerimmunol.3.053.
Significant progress has been made in the advancement of immune system modulation for cancer treatment in recent years. In particular, immune checkpoint inhibitors and chimeric antigen receptor (CAR) T-cell therapy have demonstrated remarkable clinical benefit in relapsed/refractory cancers. However, our understanding of the immuno-oncologic landscape in pediatric solid tumors remains limited and is a barrier to continued progress. We examined the immunohistochemical expression of checkpoint receptors PD-1, TIM-3, LAG-3 and their respective ligands in various pediatric cancers at diagnosis and found high expression of TIM-3/Galectin-9 in the infiltrating cells of Ewing sarcoma. Location of checkpoint receptor/ligand expressions is important, as some staining patterns were only seen along tumor borders. Finally, peripheral T cell function varied significantly among different tumors supporting a complex relationship between the tumor microenvironment and the global immune system.
近年来，免疫系统调节在癌症治疗方面取得了重大进展。特别是，免疫检查点抑制剂和嵌合抗原受体（CAR）T细胞疗法在复发/难治性癌症中已显示出显著的临床益处。然而，我们对小儿实体瘤免疫肿瘤格局的了解仍然有限，这是持续进展的一个障碍。我们检测了各种小儿癌症在诊断时检查点受体PD-1、TIM-3、LAG-3及其各自配体的免疫组化表达，发现尤因肉瘤浸润细胞中TIM-3/半乳糖凝集素-9表达较高。检查点受体/配体表达的位置很重要，因为一些染色模式仅在肿瘤边界处可见。最后，不同肿瘤之间外周T细胞功能差异显著，这支持了肿瘤微环境与整体免疫系统之间的复杂关系。
