Expression of 4-1Bb and Its Ligand on Blasts Correlates with Prognosis of Patients with Aml

Abstract

Costimulatory ligands (COLs) and their receptors (COR) regulate immune reactions and cellular survival and might be relevant in acute myeloid leukemia (AML). This study evaluated the clinical relevance of 4-1BBL, glucocorticoid-induced TNFR-related protein (GITR) and ligand (GITRL), CD80, and CD86 in case of expression on AML blasts. 98 patients were evaluated at initial diagnosis. Immunophenotypically evaluated specific fluorescence index (SFI) levels of COR and COL on blasts were correlated with morphological, cytogenetic, and several prognostic parameters. Significantly higher COR expression was seen in monocytic versus non-monocytic AML subtypes; GITR, p=0.05; GITRL, p=0.005; CD86, p=0.001). Cut-off values for two COR and their ligands were evaluated: cases presenting with 4-1BB values above cut-off 1.2 SFI levels correlated (tendentially) significantly with a higher probability for disease-free survival (DFS, p=0.06) and a favorable HR of 0.2; p=0.04 for relapse. HR for death was also significantly lower in this group (0.12; p=0.04). In contrast, a lower probability for DFS and overall survival was seen in cases with 4-1BBL expression above 2.2 SFI levels (p=0.08 and p=0.09). In addition, multivariate analysis showed a significantly higher probability of death in this group (HR 10.3, p=0.04). Expression of CD80 and CD86 did not show significant prognostic relevance. On initial diagnosis, 4-1BB and 4-1BBL qualify as markers for prediction of patients' course and represent a valuable screening target for patients with AML at initial diagnosis.

Immunoprofiling of 4-1BB Expression Predicts Outcome in Chronic Lymphocytic Leukemia (CLL)

“…This is supported by our finding that patients with high 4-1BB expression on CLL B cells have a shorter OS. This is in contrast to data on 4-1BB on AML blasts [47] and might be explained by the different disease biology.…”

Expression and prognosis of the B7 family in acute myeloid leukemia

“…As previously reported, CD80 and CD86 expression in group I of the B7 family on AML blasts do not exhibit significant prognostic relevance (31), while ICOSL expression in AML cells influences survival by driving regulatory T cells expansion (11). In AML patients, an association was identified between highly expressed PD-L1, PD-L2, and PD-1 in group II of the B7 family and poor OS (32).…”

The features of circulating and tumor-infiltrating γδ T cells in melanoma patients display critical perturbations with prognostic impact on clinical outcome

“…Of note, one study reported that the expression of 41BBL could predict patient outcome in acute myeloid leukemia. 42 Our work revealed that PD1, 41BB/41BBL, TIM3, and LAG3 are crucial checkpoints on γδT cells allowing immune escape and tumor progression. These observations thus pointed out that γδT cells may be interesting cells to look at in the context of current immunotherapies with immune checkpoint blockers, as they displayed a perturbed immune checkpoint panel expression and could be targeted by these therapies.…”