Transcriptional profiles of the Hodgkin lymphoma tumor-associated macrophage in vitro models

However, detailed features and functions of cHL TAMs and their therapeutic vulnerabilities remain largely unknown. To gain deeper insight into the biology of TAMs in cHL, we analyzed diagnostic biopsies by Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE-seq) and assessed transcriptional, proteomic and metabolic profiles of the in vitro TAM models.

We show that Reed-Sternberg (RS) cells of cHL induce disease-specific TAM phenotype, characterized by elevated expression of factors involved in chemotaxis, angiogenesis, extracellular matrix remodeling and tumor immune escape. Importantly, RS cell-conditioned TAMs expressed TGFβ, CCL17 and tryptophan catabolizing enzymes, IDO1 and IL4I1, facilitating induction or and/or recruitment of Tregs. In addition, we identified PIM1/2/3 kinases in cHL TAMs.