Distinct cell state ecosystems for nodular lymphocyte-predominant Hodgkin lymphoma
Abstract
Abstract 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.
Article Details
Authors (34)
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