Increased PD-1/STAT1 ratio may account for the survival benefit in decitabine therapy for lower risk myelodysplastic syndrome.
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.
a Department of Hematology , Shanghai Jiao Tong University Affiliated Sixth People's Hospital , Shanghai , China.
Zheng
Z
Zhang
a Department of Hematology , Shanghai Jiao Tong University Affiliated Sixth People's Hospital , Shanghai , China.
Chun-Kang
CK
Chang
a Department of Hematology , Shanghai Jiao Tong University Affiliated Sixth People's Hospital , Shanghai , China.
Qi
Q
He
a Department of Hematology , Shanghai Jiao Tong University Affiliated Sixth People's Hospital , Shanghai , China.
Juan
J
Guo
a Department of Hematology , Shanghai Jiao Tong University Affiliated Sixth People's Hospital , Shanghai , China.
Ying
Y
Tao
a Department of Hematology , Shanghai Jiao Tong University Affiliated Sixth People's Hospital , Shanghai , China.
Ling-Yun
LY
Wu
a Department of Hematology , Shanghai Jiao Tong University Affiliated Sixth People's Hospital , Shanghai , China.
Feng
F
Xu
a Department of Hematology , Shanghai Jiao Tong University Affiliated Sixth People's Hospital , Shanghai , China.
Dong
D
Wu
a Department of Hematology , Shanghai Jiao Tong University Affiliated Sixth People's Hospital , Shanghai , China.
Li-Yu
LY
Zhou
a Department of Hematology , Shanghai Jiao Tong University Affiliated Sixth People's Hospital , Shanghai , China.
Ji-Ying
JY
Su
a Department of Hematology , Shanghai Jiao Tong University Affiliated Sixth People's Hospital , Shanghai , China.
Lu-Xi
LX
Song
a Department of Hematology , Shanghai Jiao Tong University Affiliated Sixth People's Hospital , Shanghai , China.
Chao
C
Xiao
a Department of Hematology , Shanghai Jiao Tong University Affiliated Sixth People's Hospital , Shanghai , China.
Xiao
X
Li
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D001374:Azacitidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D060890:B7-H1 Antigen / Q000235:genetics / Q000378:metabolism; D015415:Biomarkers; D016516:CD4-CD8 Ratio; D000077209:Decitabine; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality*; D011379:Prognosis; D061026:Programmed Cell Death 1 Receptor / Q000235:genetics / Q000378:metabolism*; D016016:Proportional Hazards Models; D050794:STAT1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism; D016896:Treatment Outcome; D055815:Young Adult
D000964:Antimetabolites, Antineoplastic; D060890:B7-H1 Antigen; D015415:Biomarkers; C423236:CD274 protein, human; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D000077209:Decitabine; D001374:Azacitidine
Myelodysplastic syndrome; PD-1/STAT1; decitabine; lower risk