Abstract

Galectin-9 (Gal-9) expression can be negatively or positively associated with cancer patient prognosis, depending on the cancer type. However, the nature of this relationship remains unclear in multiple myeloma. Therefore, we evaluated the prognostic value of Gal-9 and its relationship with the expression of PD-L1 molecule, the most widely studied immune checkpoint inhibitor, in patients with newly diagnosed multiple myeloma. Gal-9 and PD-L1 levels in bone marrow aspirate samples were evaluated using immunofluorescence assays. Gal-9 positivity was defined as having ≥1% Gal-9-expressing plasma cells. PD-L1 expression was categorized as low or high based on its median value. The median OS of patients with positive and negative Gal-9 expression was 42 months and not reached, respectively. However, no significant difference was observed in OS between the two groups (P = 0.10). Patients with high PD-L1 expression had OS times of 14 and 43 months in the positive and negative Gal-9 expression groups, respectively. In the high PD-L1 expression group, patients expressing Gal-9 had significantly worse OS than those negative for it (P = 0.019). Multivariable Cox analysis confirmed that Gal-9 expression could independently predict shortened OS (hazard ratio, 1.090; 95% confidence interval, 1.015–1.171; P = 0.018) in patients with high PD-L1 expression. However, in the low PD-L1 expression group, patients with high Gal-9 expression exhibited a trend toward better OS (P = 0.816). Our results indicate that the prognostic value of Gal-9 may be related to PD-L1 expression in patients with newly diagnosed multiple myeloma.

Highlights

  • Galectin-9 (Gal-9) is differentially expressed in tissues involved in the immune system [1]

  • The mean PDL1 values in patients with positive (n = 22) and negative (n = 87) Gal-9 expression were 10.39 and 10.96, respectively (Figure 2C), with no significant difference observed between the two groups (P = 0.727)

  • Positive Gal-9 expression in bone marrow plasma cells was associated with poor overall survival (OS) in patients with high PD-L1 expression, and negative Gal-9 expression showed a trend toward better OS in the high PD-L1 expression group

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Summary

Introduction

Galectin-9 (Gal-9) is differentially expressed in tissues involved in the immune system [1]. Previous studies have suggested an inverse correlation between Gal-9 expression and cancer progression in several solid tumors, including breast, gallbladder, and colon cancers, as well as cervical squamous cell carcinoma and hepatocellular carcinoma [3, 5,6,7,8]. Gal-9 has been implicated in tumor immune evasion [11] by inducing apoptosis of Tim-3positive T cells [12, 13], and regulating T cell activity via death receptor 3 signaling, which is known to promote immune evasion [14] Considering these heterogeneous impacts of Gal on cancer immunity, the effects of its expression on cancer progression remain unclear

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