Increased Plasma Soluble PD-1 Concentration Correlates with Disease Progression in Patients with Cancer Treated with Anti-PD-1 Antibodies

被引：28

作者：

Ohkuma, Ryotaro ^{[1
,2
]}

Ieguchi, Katsuaki ^{[1
,3
]}

Watanabe, Makoto ^{[1
,3
]}

Takayanagi, Daisuke ^{[1
,2
,3
]}

Goshima, Tsubasa ^{[1
,2
,3
]}

Onoue, Rie ^{[1
,3
]}

Hamada, Kazuyuki ^{[2
]}

Kubota, Yutaro ^{[2
]}

Horiike, Atsushi ^{[2
]}

Ishiguro, Tomoyuki ^{[2
]}

Hirasawa, Yuya ^{[2
]}

Ariizumi, Hirotsugu ^{[2
]}

Tsurutani, Junji ^{[2
,4
]}

Yoshimura, Kiyoshi ^{[2
,3
,5
]}

Tsuji, Mayumi ^{[6
,7
]}

Kiuchi, Yuji ^{[6
,7
]}

Kobayashi, Shinichi ^{[3
]}

Tsunoda, Takuya ^{[2
]}

Wada, Satoshi ^{[1
,2
,3
]}

机构：

[1] Showa Univ, Clin Res Inst Clin Pharmacol & Therapeut, Dept Clin Diagnost Oncol, Setagaya Ku, 6-11-11,Kitakarasuyama, Tokyo 1578577, Japan

[2] Showa Univ, Sch Med, Dept Med, Div Med Oncol,Shinagawa Ku, Tokyo 1428555, Japan

[3] Showa Univ, Clin Res Inst Clin Pharmacol & Therapeut, Setagaya Ku, 6-11-11,Kitakarasuyama, Tokyo 1578577, Japan

[4] Showa Univ, Adv Canc Translat Res Inst, Shinagawa Ku, 1-5-8,Hatanodai, Tokyo 1428555, Japan

[5] Showa Univ, Clin Res Inst Clin Pharmacol Therapeut, Dept Clin Immuno Oncol, Setagaya Ku, 6-11-11,Kitakarasuyama, Tokyo 1578577, Japan

[6] Showa Univ, Sch Med, Dept Pharmacol, Div Med Pharmacol,Shinagawa Ku, 1-5-8,Hatanodai, Tokyo 1428555, Japan

[7] Showa Univ, Pharmacol Res Ctr, Shinagawa Ku, 1-5-8,Hatanodai, Tokyo 1428555, Japan

来源：

BIOMEDICINES | 2021年 / 9卷 / 12期

关键词：

biomarkers; immune checkpoint inhibitors; anti-programmed death-1 (PD-1); PROGNOSTIC-SIGNIFICANCE; LUNG; PEMBROLIZUMAB; EXPRESSION; NIVOLUMAB; BLOCKADE;

D O I：

10.3390/biomedicines9121929

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Immune checkpoint inhibitors (ICIs) confer remarkable therapeutic benefits to patients with various cancers. However, many patients are non-responders or develop resistance following an initial response to ICIs. There are no reliable biomarkers to predict the therapeutic effect of ICIs. Therefore, this study investigated the clinical implications of plasma levels of soluble anti-programmed death-1 (sPD-1) in patients with cancer treated with ICIs. In total, 22 patients (13 with non-small-cell lung carcinoma, 8 with gastric cancer, and 1 with bladder cancer) were evaluated for sPD-1 concentration using enzyme-linked immunosorbent assays for diagnostic and anti-PD-1 antibody analyses. sPD-1 levels were low before the administration of anti-PD-1 antibodies. After two and four cycles of anti-PD-1 antibody therapy, sPD-1 levels significantly increased compared with pretreatment levels (p = 0.0348 vs. 0.0232). We observed an increased rate of change in plasma sPD-1 concentrations after two and four cycles of anti-PD-1 antibody therapy that significantly correlated with tumor size progression (p = 0.024). sPD-1 may be involved in resistance to anti-PD-1 antibody therapy, suggesting that changes in sPD-1 levels can identify primary ICI non-responders early in treatment. Detailed analysis of each cancer type revealed the potential of sPD-1 as a predictive biomarker of response to ICI treatment in patients with cancer.

引用

页数：13

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