Single-cell profiling reveals the importance of CXCL13/CXCR5 axis biology in lymphocyte-rich classic Hodgkin lymphoma
Tomohiro Aoki, Lauren C. Chong, Katsuyoshi Takata, Katy Milne, Ashley Marshall, Elizabeth A. Chavez, Tomoko Miyata‐Takata, Susana Ben‐Neriah, Doria Unrau, Adèle Telenius, Merrill Boyle, Andrew P. Weng, Kerry J. Savage, David W. Scott, Pedro Farinha, Sohrab P. Shah, Brad H. Nelson, Christian Steidl
Abstract
Significance Our study provides detailed functional and spatial characteristics of immune cells in the LR-CHL microenvironment at single-cell resolution. We describe detailed T cell subset definitions and importantly identified a unique CD4 + PD-1 + CXCL13 + CXCR5 − TFH-like subset that surrounds HRS cells, appears in close proximity to CXCR5 + B cells, and is associated with poor clinical outcome. We also uncovered unique PD-1/PD-L1 axis biology in LR-CHL, namely a negative correlation between PD-L1 genetic alterations on HRS cells and PD-1 protein expression in the tumor microenvironment. Importantly, our findings contribute to a deeper understanding of cellular cross-talk in LR-CHL, which may aid in the development of novel biomarkers and targeted treatment strategies.