biostudies-literatureKarihtala KCancer Foundation Finland sr1919-1931https://www.ebi.ac.uk/biostudies/studies/S-EPMC8941476biostudies-literatureUnknown6(6)Emerging evidence indicates a major impact for the tumor microenvironment (TME) and immune escape in the pathogenesis and clinical course of classical Hodgkin lymphoma (cHL). We used gene expression profiling (n = 88), CIBERSORT, and multiplex immunohistochemistry (n = 131) to characterize the immunoprofile of cHL TME and correlated the findings with survival. Gene expression analysis divided tumors into subgroups with T cell-inflamed and -noninflamed TME. Several macrophage-related genes were upregulated in samples with the non-T cell-inflamed TME, and based on the immune cell proportions, the samples clustered according to the content of T cells and macrophages. A cluster with high proportions of checkpoint protein (programmed cell death protein 1, PD-1 ligands, indoleamine 2,3 dioxygenaBlood advancesCheckpoint protein expression in the tumor microenvironment defines the outcome of classical Hodgkin lymphoma patients.PMC8941476120102160092180125200088140136210047130117110094Karihtala KSteidl CKarjalainen-Lindsberg MLChan FCPellinen TLeppa SLeivonen SKfalseCheckpoint protein expression in the tumor microenvironment defines the outcome of classical Hodgkin lymphoma patients.Emerging evidence indicates a major impact for the tumor microenvironment (TME) and immune escape in the pathogenesis and clinical course of classical Hodgkin lymphoma (cHL). We used gene expression profiling (n = 88), CIBERSORT, and multiplex immunohistochemistry (n = 131) to characterize the immunoprofile of cHL TME and correlated the findings with survival. Gene expression analysis divided tumors into subgroups with T cell-inflamed and -noninflamed TME. Several macrophage-related genes were upregulated in samples with the non-T cell-inflamed TME, and based on the immune cell proportions, the samples clustered according to the content of T cells and macrophages. A cluster with high proportions of checkpoint protein (programmed cell death protein 1, PD-1 ligands, indoleamine 2,3 dioxygena2022-01-01T00:00:00Z2022 Mar2026-03-27T16:40:50.047Z2025-04-03T21:30:43.085ZS-EPMC89414763494199010.1182/bloodadvances.2021006189