将免疫化疗作为诱导治疗成分的联合治疗策略是当前治疗高危转移性局部晚期鼻咽癌（NPC）的趋势之一。然而，单细胞水平反应异质性背后的机制尚未得到充分探索。对初治高危局部转移患者的治疗前和治疗中配对样本进行了 18 个批量和 11 个单细胞 RNA 测序获得高级NPC。质量控制后，总共 87 191 个细胞被纳入后续生物信息学分析。免疫化疗与治疗中的肿瘤微环境 (TME) 重塑相关，包括抗 TME 特征上调、亲 TME 特征下调、逆转 CD8 T疲劳和重新极化促炎 TAM。对于达到完全缓解的患者，CD8 T细胞的细胞毒活性被刺激，并提供更多的干扰素-γ，这将是TAM促炎复极化的关键，最终反过来促进CD8 T细胞成熟。在未达到完全缓解的患者中，治疗后内皮细胞的分化和缺氧特征升高。这些患者在基线（治疗前）的恶性细胞中表现出较高水平的免疫检查点基因，并且肿瘤抗原呈递活性降低，这可能是治疗耐药机制的基础。这项研究描绘了基于免疫化疗的联合诱导后 TME 调节的图谱免疫化疗重塑了 T 细胞表型。对于达到完全缓解的患者，治疗后CD8 T细胞会提供更多的干扰素γ，这将是TAM促炎复极化的关键，并最终促进CD8 T细胞成熟。在未达到完全缓解的患者中，恶性细胞在治疗前表现出较高水平的免疫检查点基因，并且肿瘤抗原呈递活性降低，这可能是治疗耐药机制的基础。© 2024 作者。约翰·威利出版的《临床与转化医学》

Combinatory therapeutic strategy containing immunochemotherapy as part of induction therapy components is one of the current trends in the treatment of high-risk metastatic locally advanced nasopharyngeal carcinoma (NPC). However, the mechanism underlying the heterogeneity of response at the single-cell level has not been underexplored.18 bulks and 11 single-cell RNA sequencing from paired before-treatment and on-treatment samples in patients with treatment-naive high-risk metastatic locally advanced NPCs were obtained. Following quality control, a total of 87 191 cells were included in the subsequence bioinformatics analysis.Immunochemotherapy was associated with on-treatment tumour microenvironment (TME) remodelling, including upregulation of anti-TMEs signatures, downregulation of pro-TMEs signatures, reversing CD8+ T exhaustion, and repolarizing proinflammatory TAMs. For the patients achieving a complete response, the cytotoxic activity of CD8+ T cells was stimulated and more interferon-gamma was provided, which would be the key for TAMs proinflammatory repolarization and eventually promote the CD8+ T cells maturation in turn. Among patients who did not reach complete response, differentiation and hypoxia signatures for endothelial cells were elevated after therapy. These patients exhibited higher levels of immune checkpoint genes in malignant cells at the baseline (before treatment), and decreased tumour antigen presentation activity, which may underlie the resistance mechanism to therapy.This study pictures a map of TME modulation following immunochemotherapy-based combination induction therapy and provides potential future approaches.Immunochemotherapy remodeled T cell phenotypes. For the patients achieving complete response, more interferon gamma was provided by CD8+ T cells after therapy, which would be the key for TAMs pro-inflammatory repolarization and eventually promote the CD8+ T cells maturation in turns. Among patients who did not reach complete response, malignant cells exhibited higher level of immune checkpoint genes before therapy, and decreased tumor antigen presentation activity, which may underlie the resistance mechanism to therapy.© 2024 The Author(s). Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.