Scholarlink

<p>Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy, yet most patients fail to achieve durable responses. To better understand the tumor microenvironment (TME), we analyze single-cell RNA-seq (~189 K cells) from 36 metastatic melanoma samples, defining 14 cell types, 55 subtypes, and 15 transcriptional hallmarks of malignant cells. Correlations between cell subtype proportions reveal six distinct clusters, with a mature dendritic cell subtype enriched in immunoregulatory molecules (mregDC) linked to naive T and B cells. Importantly, mregDC abundance predicts progression-free survival (PFS) with ICIs and other therapies, especially when combined with the TCF7 + /– CD8 T cell ratio. Analysis of an independent cohort (n = 318) validates mregDC as a predictive biomarker for anti-CTLA-4 plus anti-PD-1 therapies. Further characterization of mregDCs versus conventional dendritic cells (cDC1/cDC2) highlights their unique transcriptional, epigenetic (single-nucleus ATAC-seq data for cDCs from 14 matched samples), and interaction profiles, offering new insights for improving immunotherapy response and guiding future combination treatments.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Mature and migratory dendritic cells promote immune infiltration and response to anti-PD-1 checkpoint blockade in metastatic melanoma

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年9月1日

查看全文
  • Jiekun Yang,
  • Cassia Wang,
  • Doris Fu,
  • Li-Lun Ho,
  • Kyriakitsa Galani,
  • Lee Chen,
  • Jose Gonzalez,
  • Jolene Fu,
  • Amy Y. Huang,
  • Dennie T. Frederick,
  • Liang He,
  • Mukta Asnani,
  • Rahul Tacke,
  • Emily J. Robitschek,
  • Sandeep K. Yadav,
  • Wentao Deng,
  • Kelly P. Burke,
  • Tatyana Sharova,
  • Ryan J. Sullivan,
  • Sarah Weiss,
  • Kunal Rai,
  • David Liu,
  • Genevieve M. Boland,
  • Manolis Kellis

摘要

Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy, yet most patients fail to achieve durable responses. To better understand the tumor microenvironment (TME), we analyze single-cell RNA-seq (~189 K cells) from 36 metastatic melanoma samples, defining 14 cell types, 55 subtypes, and 15 transcriptional hallmarks of malignant cells. Correlations between cell subtype proportions reveal six distinct clusters, with a mature dendritic cell subtype enriched in immunoregulatory molecules (mregDC) linked to naive T and B cells. Importantly, mregDC abundance predicts progression-free survival (PFS) with ICIs and other therapies, especially when combined with the TCF7 + /– CD8 T cell ratio. Analysis of an independent cohort (n = 318) validates mregDC as a predictive biomarker for anti-CTLA-4 plus anti-PD-1 therapies. Further characterization of mregDCs versus conventional dendritic cells (cDC1/cDC2) highlights their unique transcriptional, epigenetic (single-nucleus ATAC-seq data for cDCs from 14 matched samples), and interaction profiles, offering new insights for improving immunotherapy response and guiding future combination treatments.