Hodgkin lymphoma (HL) is characterized by an extensively dominant tumor microenvironment (TME) composed of different types of non-cancerous immune cells with rare malignant cells. Characterization of the cellular components and… Click to show full abstract
Hodgkin lymphoma (HL) is characterized by an extensively dominant tumor microenvironment (TME) composed of different types of non-cancerous immune cells with rare malignant cells. Characterization of the cellular components and their spatial relationship is crucial to understanding crosstalk and therapeutic targeting in the TME. We performed single-cell RNA sequencing of more than 127,000 cells from 22 HL tissue specimens and 5 reactive lymph nodes, profiling for the first time the phenotype of the HL-specific immune microenvironment at single-cell resolution. Single-cell expression profiling identified a novel HL-associated subset of T cells with prominent expression of the inhibitory receptor LAG3, and functional analyses established this LAG3+ T cell population as a mediator of immunosuppression. Multiplexed spatial assessment of immune cells in the microenvironment also revealed increased LAG3+ T cells in the direct vicinity of MHC class-II deficient tumor cells. Our findings provide novel insights into TME biology and suggest new approaches to immune checkpoint targeting in HL.
               
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