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. 2020 Nov 23;137(18):2463–2480. doi: 10.1182/blood.2019004547

Figure 6.

Figure 6.

HAVCR2-LGALS9 interactions on dysfunctional CD8+ T cells and leukemic blasts. (A) Violin plots depict expression of coinhibitory receptors (on dysfunctional CD8+ T cells, shown as open circles) and their interacting ligands (on malignant T-ALL cells, depicted as triangles). Colors represent malignant clusters based on PAGODA2 (Figure 1). Each box corresponds to expression of the indicated coinhibitory receptor-ligand combination. (B) Receptor-ligand interaction scores inferred from expression of receptors (in CD8+ T cells) and ligands (in T-ALL cells), respectively, pointing toward prominent HAVCR2-LGALS9 interaction. (C) IHC of LGALS9 and HAVCR2 on bone marrow from representative ETP-ALL patient (P2) demonstrates strong staining of LGALS9 on leukemic blasts and interspersed HAVCR2 staining on microenvironmental cells (magnification ×60). (D) Intracellular immunofluorescent staining of LGALS9 and isotype control in DND-41 T-ALL cells. (E) mRNA expression of T-cell dysfunction markers (HAVCR2 and TIGIT) and effector cytokines (GZMB, IL-2, and IFNγ) on normal donor activated CD8+ T cells cultured with T-ALL supernatant vs control media. *P < .05, **P < .01, ***P < .001, averaged from 3 technical replicates using 2-sided Student t test.