Increased PD-1/STAT1 ratio may account for the survival benefit in decitabine therapy for lower risk myelodysplastic syndrome

Leuk Lymphoma. 2017 Apr;58(4):969-978. doi: 10.1080/10428194.2016.1219903. Epub 2016 Aug 11.

Abstract

Decitabine is an effective therapy for patients with lower risk myelodysplastic syndrome (MDS). However, the mechanisms of decitabine's therapeutic effect are not well established. Forty-four lower risk MDS patients received decitabine therapy. 59.1% patients achieved treatment response, and 53.8% patients who were RBC/platelet-dependent cast off the transfusion burden. The median overall survival (OS) was 19.0 months after decitabine treatment. Moreover, polarization toward type 1 in the CD8 + subset was enhanced, and a significantly increased expression of the PD-1, PD-L1, and PD-1/STAT1 ratio was observed in these lower risk MDS. The patients with amplification of PD-1/STAT1 ratio (2-4) achieved longer OS. Thus, our results suggest that the effect mechanism of decitabine toward lower risk MDS may be the moderate increase of PD-1/STAT1, which contributes to hematopoietic improvement. These findings suggest that a different PD-1-related strategy from those used to treat higher risk patients could be used for lower risk MDS patients.

Keywords: Myelodysplastic syndrome; PD-1/STAT1; decitabine; lower risk.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antimetabolites, Antineoplastic / administration & dosage
  • Antimetabolites, Antineoplastic / adverse effects
  • Antimetabolites, Antineoplastic / therapeutic use
  • Azacitidine / administration & dosage
  • Azacitidine / adverse effects
  • Azacitidine / analogs & derivatives
  • Azacitidine / therapeutic use
  • B7-H1 Antigen / genetics
  • B7-H1 Antigen / metabolism
  • Biomarkers
  • CD4-CD8 Ratio
  • Decitabine
  • Female
  • Gene Expression
  • Humans
  • Male
  • Middle Aged
  • Myelodysplastic Syndromes / diagnosis
  • Myelodysplastic Syndromes / drug therapy
  • Myelodysplastic Syndromes / metabolism*
  • Myelodysplastic Syndromes / mortality*
  • Prognosis
  • Programmed Cell Death 1 Receptor / genetics
  • Programmed Cell Death 1 Receptor / metabolism*
  • Proportional Hazards Models
  • STAT1 Transcription Factor / genetics
  • STAT1 Transcription Factor / metabolism*
  • T-Lymphocytes / metabolism
  • Treatment Outcome
  • Young Adult

Substances

  • Antimetabolites, Antineoplastic
  • B7-H1 Antigen
  • Biomarkers
  • CD274 protein, human
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • STAT1 Transcription Factor
  • STAT1 protein, human
  • Decitabine
  • Azacitidine