Impact of acetaminophen on the efficacy of immunotherapy in cancer patients

被引：31

作者：

Bessede, A. ^{[1
]}

Marabelle, A. ^{[2
,3
]}

Guegan, J. P. ^{[1
]}

Danlos, F. X. ^{[2
,3
]}

Cousin, S. ^{[4
]}

Peyraud, F. ^{[1
,2
,3
]}

Chaput, N. ^{[5
,6
,7
,8
]}

Spalato, M. ^{[4
]}

Roubaud, G. ^{[4
]}

Cabart, M. ^{[4
]}

Khettab, M. ^{[9
]}

Chaibi, A. ^{[1
]}

Rey, C. ^{[1
]}

Nafia, I ^{[1
]}

Mahon, F. X. ^{[4
,9
]}

Soria, J. C. ^{[10
]}

Italiano, A. ^{[2
,3
,4
,9
]}

机构：

[1] Explicyte, Bordeaux, France

[2] Univ Paris Saclay, Gustave Roussy, INSERM U1015, DITEP Drug Dev Dept, Villejuif, France

[3] Univ Paris Saclay, Gustave Roussy, CIC1428, Villejuif, France

[4] Inst Bergonie, Dept Med, Bordeaux, France

[5] Gustave Roussy Canc Campus, Lab Immunomonitoring Oncol, CNRS UMS 3655, Villejuif, France

[6] INSERM US23, Villejuif, France

[7] Univ Paris Saclay, Fac Pharm, Chatenay Malabry, France

[8] Univ Paris Saclay, Lab Genet Instabil & Oncogenesis, UMR CNRS 8200, Gustave Roussy, Villejuif, France

[9] Univ Bordeaux, Fac Med, Bordeaux, France

[10] Gustave Roussy, Dept Med, Villejuif, France

来源：

ANNALS OF ONCOLOGY | 2022年 / 33卷 / 09期

关键词：

acetaminophen; immune checkpoint inhibitors; immunotherapy; cancer; REGULATORY T-CELLS; IMMUNE; PARACETAMOL; RESPONSES; TUMORS; TH17;

D O I：

10.1016/j.annonc.2022.05.010

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: Acetaminophen (APAP) use has been associated with blunted vaccine immune responses. This study aimed to assess APAP impact on immunotherapy efficacy in patients with cancer. Patients and methods: Exposure to APAP was assessed by plasma analysis and was correlated with clinical outcome in three independent cohorts of patients with advanced cancer who were treated with immune checkpoint blockers (ICBs). The immunomodulatory effects of APAP were evaluated on a preclinical tumor model and on human peripheral blood mononuclear cells (PBMCs) from healthy donors. Results: Detectable plasma APAP levels at treatment onset were associated with a significantly worse clinical outcome in ICB-treated cancer patients, independently of other prognostic factors. APAP significantly reduced ICB efficacy in the preclinical MC38 model, as well as the production of PD-1 blockade-related interferon -g secretion by human PBMCs. Moreover, reduction of ICB efficacy in vivo was associated with significantly increased tumor infiltration by regulatory T cells (Tregs). Administration of APAP over 24 h induced a significant expansion of peripheral Tregs in healthy individuals. In addition, interleukin-10, a crucial mediator of Treg-induced immune suppression, was significantly up-regulated upon treatment with ICB in cancer patients taking APAP. Conclusions: This study provides strong preclinical and clinical evidence of the role of APAP as a potential suppressor of antitumor immunity. Hence, APAP should be used with caution in patients treated with ICB.

引用

页码：909 / 915

页数：7

共 29 条

[21] Effect of prophylactic paracetamol administration at time of vaccination on febrile reactions and antibody responses in children: two open-label, randomised controlled trials [J].