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Background <p>Diffuse large B-cell lymphoma (DLBCL) is a biologically heterogeneous lymphoma with variable treatment outcomes. Immune checkpoints are key regulators of tumor-immune interactions and important targets in cancer therapy. This study investigates the roles of <i>PD-1</i>, <i>PD-L1</i>, and <i>CTLA-4</i> gene polymorphisms, along with their mRNA and protein expression, in DLBCL pathogenesis.</p> Methods <p>This case–control study included 20 patients with newly diagnosed DLBCL and 20 age- and sex-matched healthy controls. SNPs in <i>PD-1</i> (rs2227981), <i>PD-L1</i> (rs4143815), and <i>CTLA-4</i> (rs231775) were genotyped. Gene expression was assessed via RT-qPCR, and protein levels on immune cells were analyzed by flow cytometry.</p> Results <p><i>PD-1</i>, <i>PD-L1</i>, and <i>CTLA-4</i> mRNA levels were significantly elevated in DLBCL patients (<i>p</i> = 0.018, <i>p</i> = 0.006, <i>p</i> = 0.031, respectively). These SNPs were associated with expression changes (PD-1: <i>p</i> = 0.009; PD-L1: <i>p</i> = 0.007; CTLA-4: <i>p</i> = 0.018). Flow cytometry showed elevated percentages of CD4⁺PD-1⁺ (<i>p</i> = 0.010) and CD4⁺PD-L1⁺ (<i>p</i> = 0.002) cells in patients. No significant clinical differences were found among DLBCL subtypes.</p> Conclusion <p>These results suggest that overexpression of these checkpoints and related genetic variants may contribute to immune escape and disease progression in DLBCL. PD-1, PD-L1, and CTLA-4 may serve as potential biomarkers for prognosis and personalized therapy. Further large-scale studies are needed to confirm these findings.</p>

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Polymorphisms and overexpression of immune checkpoints PD-1, PD-L1, and CTLA-4 in DLBCL: biomarker insights from a case–control study

  • 期刊论文

  • 发表日期：

    2026年3月5日

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  • Habibe Sema Arslan Unal,
  • Ozan Salim,
  • Unal Atas,
  • Sule Darbas Aras,
  • Nurten Sayin Ekinci,
  • Yahya Kilinc,
  • Fahri Ucar

摘要

Background

Diffuse large B-cell lymphoma (DLBCL) is a biologically heterogeneous lymphoma with variable treatment outcomes. Immune checkpoints are key regulators of tumor-immune interactions and important targets in cancer therapy. This study investigates the roles of PD-1, PD-L1, and CTLA-4 gene polymorphisms, along with their mRNA and protein expression, in DLBCL pathogenesis.

Methods

This case–control study included 20 patients with newly diagnosed DLBCL and 20 age- and sex-matched healthy controls. SNPs in PD-1 (rs2227981), PD-L1 (rs4143815), and CTLA-4 (rs231775) were genotyped. Gene expression was assessed via RT-qPCR, and protein levels on immune cells were analyzed by flow cytometry.

Results

PD-1, PD-L1, and CTLA-4 mRNA levels were significantly elevated in DLBCL patients (p = 0.018, p = 0.006, p = 0.031, respectively). These SNPs were associated with expression changes (PD-1: p = 0.009; PD-L1: p = 0.007; CTLA-4: p = 0.018). Flow cytometry showed elevated percentages of CD4⁺PD-1⁺ (p = 0.010) and CD4⁺PD-L1⁺ (p = 0.002) cells in patients. No significant clinical differences were found among DLBCL subtypes.

Conclusion

These results suggest that overexpression of these checkpoints and related genetic variants may contribute to immune escape and disease progression in DLBCL. PD-1, PD-L1, and CTLA-4 may serve as potential biomarkers for prognosis and personalized therapy. Further large-scale studies are needed to confirm these findings.