Plasma soluble programmed death ligand 1 levels predict clinical response in peripheral T-cell lymphomas

Hematol Oncol. 2019 Aug;37(3):270-276. doi: 10.1002/hon.2636. Epub 2019 May 30.

Abstract

Immune checkpoints, including PD-1/PD-L1, play an important role in immunosuppression in various malignancies. Elevated levels of soluble programmed death ligand 1 (sPD-L1) are associated with worse prognosis in multiple myeloma and diffuse large B cell lymphoma. Herein, the purpose of this study is to investigate the relationships between plasma sPD-L1 levels and clinical response in peripheral T-cell lymphoma (PTCL) patients. A total of 37 PTCL patients and 20 healthy volunteers were enrolled. Peripheral blood from patients was collected prior to systemic therapy. Plasma levels of sPD-L1 and IFN-γ were measured by enzyme-linked immunosorbent assay (ELISA). PD-L1 expression in tissues was detected by immunohistochemistry (IHC). Clinical response for patients was evaluated. ONCOMINE database analyses showed that PD-L1 mRNA expression was significantly upregulated in PTCLs. The median sPD-L1 level was 0.729 ng/mL for 20 healthy volunteers and 1.696 ng/mL for 37 PTCL patients which was significantly higher than that in healthy volunteers (0.000). The sPD-L1 level was positively correlated with IFN-γ level (0.000, r = 0.849) and was also positively associated with clinical staging (0.045), LDH level (0.003), and β2-MG level (0.045). Patients with high sPD-L1 level had lower overall response rate than those with low sPD-L1 level (88.9% vs 50.0%, 0.022) and tended to have poorer PFS and OS. PD-L1 expression in tissues matched very well with the sPD-L1 level in PTCL patients. In conclusion, PTCL patients had higher sPD-L1 level compared with healthy volunteers. High sPD-L1 level was correlated with worse clinical response, suggesting that sPD-L1 level was an underlying plasma biomarker to predict the prognosis for PTCL patients.

Keywords: IFN-γ; PTCLs; clinical response; sPD-L1.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • B7-H1 Antigen / blood*
  • Biomarkers, Tumor / blood
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Healthy Volunteers
  • Humans
  • Immunohistochemistry
  • Immunosuppression Therapy
  • Immunosuppressive Agents / therapeutic use
  • Interferon-gamma / blood
  • Lymphoma, T-Cell, Peripheral / blood*
  • Lymphoma, T-Cell, Peripheral / drug therapy*
  • Male
  • Middle Aged
  • Multiple Myeloma / blood*
  • Multiple Myeloma / drug therapy*
  • Prognosis
  • Treatment Outcome
  • Young Adult

Substances

  • B7-H1 Antigen
  • Biomarkers, Tumor
  • CD274 protein, human
  • IFNG protein, human
  • Immunosuppressive Agents
  • Interferon-gamma