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<p>Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare cancer, and few studies have comprehensively investigated the immune microenvironment and rare lymphocyte-predominant (LP) cells. Here we develop a NLPHL specific lymphocyte-predominant ecotype (LPE) model to identify 34 distinct cell states across 14 cell types that co-occur within 3 LPEs for 171 cases. LPE1 and LPE2 were characterized by immunosuppressive microenvironments with high expression of <i>B2M</i> on LP cells, CD8 T-cell exhaustion, immune checkpoint genes expressed by follicular T-cells, and an improved freedom from progression compared to LPE3 in training (<i>n</i> = 109, with 65% LPE1/2) and validation cohorts (<i>n</i> = 62, with 61% LPE1/2). We validate the co-occurrence and co-localization of cell states using spatial transcriptomics. Protein expression of HLA-I and HLA-II on LP cells and SSTR2 on dendritic cells was predictive of LPE1 (C-statistic=0.69), LPE2 (C-statistic=0.79), and LPE3 (C-statistic=0.60). This study establishes a clinically relevant biologic categorization for NLPHL.</p>

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Distinct cell state ecosystems for nodular lymphocyte-predominant Hodgkin lymphoma

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年9月26日

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  • Ajay Subramanian,
  • Shengqin Su,
  • Jamie Flerlage,
  • Stefan Alig,
  • Sheren Younes,
  • Lianna J. Marks,
  • Chelsea Pinnix,
  • Francisco Vega,
  • Raphael Steiner,
  • Priya Kumar,
  • Heidi Mocikova,
  • Alice Sykorova,
  • Vit Prochazka,
  • Cristiane Milito,
  • Pamela Allen,
  • Darina Paulino,
  • Alan Ramsay,
  • Timothy Flerlage,
  • Monica Palese,
  • Robert West,
  • ChunFang Zhu,
  • Troy Noordenbos,
  • Joseph Schroers-Martin,
  • Shuchun Zhao,
  • Natalie J. Park,
  • Anusha Kalbasi,
  • Everett J. Moding,
  • Aaron M. Newman,
  • Ranjana H. Advani,
  • Richard T. Hoppe,
  • Maximilian Diehn,
  • Yasodha Natkunam,
  • Ash A. Alizadeh,
  • Michael Sargent Binkley

摘要

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare cancer, and few studies have comprehensively investigated the immune microenvironment and rare lymphocyte-predominant (LP) cells. Here we develop a NLPHL specific lymphocyte-predominant ecotype (LPE) model to identify 34 distinct cell states across 14 cell types that co-occur within 3 LPEs for 171 cases. LPE1 and LPE2 were characterized by immunosuppressive microenvironments with high expression of B2M on LP cells, CD8 T-cell exhaustion, immune checkpoint genes expressed by follicular T-cells, and an improved freedom from progression compared to LPE3 in training (n = 109, with 65% LPE1/2) and validation cohorts (n = 62, with 61% LPE1/2). We validate the co-occurrence and co-localization of cell states using spatial transcriptomics. Protein expression of HLA-I and HLA-II on LP cells and SSTR2 on dendritic cells was predictive of LPE1 (C-statistic=0.69), LPE2 (C-statistic=0.79), and LPE3 (C-statistic=0.60). This study establishes a clinically relevant biologic categorization for NLPHL.