Immune cell atlas of the lymphocyte-rich classic Hodgkin lymphoma microenvironment at single-cell resolution

This study provides detailed functional and spatial characteristics of immune cells in the LR-CHL microenvironment at single-cell resolution. Researchers from British Columbia (BC) Cancer 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. The researchers 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, these 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.

Immune cell atlas of the LR-CHL microenvironment at single-cell resolution

Cells from 28 CHL and 5 RLN cases were clustered using the PhenoGraph algorithm to identify groups of cells with similar expression patterns. (A) Heatmap summarizing mean expression (normalized and log transformed) of selected canonical markers in each cluster. Data have been scaled row-wise for visualization. The covariate bar on the Left side indicates the component associated with each gene, and black boxes highlight prominent expression of known subtype genes. (B) Single-cell expression of all cells from CHL and RLN in tSNE space (first two dimensions). Cells are colored according to PhenoGraph cluster. Subsets of cells from each CHL subtype are shown on the same coordinates. (C) Proportion of cells in each cluster originating from LR-CHL (light green) and other CHL (dark green) samples. The dashed white line represents the total proportion of cells from other CHL samples in the merged population. (D) The proportion of cells assigned to a given immune cell type (as determined by cluster annotation) was calculated for each sample. Boxplots summarize the distribution of the proportions for all samples, grouped by pathological subtype (LR-CHL or other CHL subtype). P values are shown Above and demonstrate a significant increase in the proportion of B cells present in LR-CHL compared to other CHL. (E and F) Boxplots summarizing the proportion of naïve (E) and memory (F) B cells relative to total cells in each sample, separated according to CHL subtype and RLNs. (G) Ratio of naïve B cells/germinal center B cells (by cluster assignment) according to pathological subtype. P values were calculated using t tests.

Aoki T, Chong LC, Takata K, Milne K, Marshall A, Chavez EA, Miyata-Takata T, Ben-Neriah S, Unrau D, Telenius A, Boyle M, Weng AP, Savage KJ, Scott DW, Farinha P, Shah SP, Nelson BH, Steidl C. (2021) Single-cell profiling reveals the importance of CXCL13/CXCR5 axis biology in lymphocyte-rich classic Hodgkin lymphoma. PNAS 118(41):e2105822118. [article]

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