Increased expression of the TIM-3–galectin-9 axis throughout disease progression in B-ALL. (A) Cartoon of the ICRs and their ligands expressed in cells. (B) Heat map showing the median protein expression (analyzed by flow cytometry) of ICRs in CD4⁺ and CD8⁺ T cells (left) and ICR ligands in leukemic blasts and MSCs (right) obtained from the BM of patients with B-ALL at Dx (n = 47) and relapse (Rel; n = 38), normalized to age-matched nonleukemic/healthy donor (HD) BM (n = 21). (C) Individual FACS mean fluorescence intensity of TIM-3 expression in CD4⁺ and CD8⁺ T cells and its ligand galectin-9 in leukemic blasts and MSCs for each B-ALL/HD BM sample analyzed. Pediatric and adult patients are color coded. The Mann-Whitney U test was used to compare the expression of ICRs and ligands between patients and HDs. ∗P ≤ .05; ∗∗P ≤ .01; ∗∗∗P ≤ .001. (D) Four-year event-free survival (EFS) of recurrent R/R patients with B-ALL (n = 64) expressing low or high LGALS9 using the TARGET data set. (E) Three-year EFS of varni-cel–treated R/R patients with B-ALL (n = 37) based on low or high TIM-3 expression in CAR⁺ T cells in the infusion product. “Low” denotes patients with LGALS9/TIM-3 levels below the median, and “high” denotes above the median. MFI, mean fluorescence intensity; Rel, relapse; varni-cel, varnimcabtagene autoleucel.