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<p>Tumor cell heterogeneity and interactions with the immune microenvironment play a key role in the progression and therapeutic efficacy of natural killer/T-cell lymphoma (NKTCL). We perform single-cell RNA sequencing analysis of 63 samples, integrating spatial transcriptomics, bulk transcriptomics, proteomics, and metabolomics to dissect inter- and intra-tumoral heterogeneity. Four meta-programs (MP) are identified, including MP1 (immune-responsive), MP2 (proliferative), MP3 (inflammatory), and MP4 (metabolic), each linked to distinct molecular and immune features. MP1 exhibits an immune-exhausted tumor microenvironment and high programmed death-ligand 1 expression, suggesting a potential response to immune checkpoint blockade. MP2 shows an immune-desert phenotype with elevated HDAC2 and MKI67 expression, indicating epigenetic regulation in tumor proliferation. MP3 is characterized by a myeloid-dominant tumor microenvironment, JAK/STAT pathway activation, and an aggressive clinical course. MP4 exhibits a distinct amino acid metabolic profile and enriched tertiary lymphoid structures. Collectively, our study provides a high-resolution molecular atlas of NKTCL heterogeneity, offering insights into patient stratification and potential avenues for future therapeutic development.</p>

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Single-cell profiling of natural killer/T-cell lymphoma reveals stratified immune features and potential therapeutic implications

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月29日

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  • Yi Cao,
  • Jun Cai,
  • Danling Dai,
  • Jinni Wang,
  • Yuchen Zhang,
  • Jie Xiong,
  • Huiqiang Huang,
  • Yan Gao,
  • Yi Xia,
  • Fang Liu,
  • Xinna Gao,
  • Shenrui Bai,
  • Qihua Zou,
  • Jiahui Wang,
  • Shuyun Ma,
  • Junfeng Jiang,
  • Weili Zhao,
  • Wenlong Zhong,
  • Qingqing Cai

摘要

Tumor cell heterogeneity and interactions with the immune microenvironment play a key role in the progression and therapeutic efficacy of natural killer/T-cell lymphoma (NKTCL). We perform single-cell RNA sequencing analysis of 63 samples, integrating spatial transcriptomics, bulk transcriptomics, proteomics, and metabolomics to dissect inter- and intra-tumoral heterogeneity. Four meta-programs (MP) are identified, including MP1 (immune-responsive), MP2 (proliferative), MP3 (inflammatory), and MP4 (metabolic), each linked to distinct molecular and immune features. MP1 exhibits an immune-exhausted tumor microenvironment and high programmed death-ligand 1 expression, suggesting a potential response to immune checkpoint blockade. MP2 shows an immune-desert phenotype with elevated HDAC2 and MKI67 expression, indicating epigenetic regulation in tumor proliferation. MP3 is characterized by a myeloid-dominant tumor microenvironment, JAK/STAT pathway activation, and an aggressive clinical course. MP4 exhibits a distinct amino acid metabolic profile and enriched tertiary lymphoid structures. Collectively, our study provides a high-resolution molecular atlas of NKTCL heterogeneity, offering insights into patient stratification and potential avenues for future therapeutic development.