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过氧化物酶体增殖物激活受体-γ 激动剂联合血管紧张素受体阻滞剂对免疫治疗患者结局的影响。

The impact of peroxisome proliferator-activated receptor-γ activating angiotensin receptor blocker on outcomes of patients receiving immunotherapy.

机构信息

Department of Medicine, Mount Auburn Hospital, Harvard Medical School, Boston, Massachusetts, USA.

Da Vinci Minimally Invasive Surgery Center, Chung Shan Medical University Hospital, Taichung, Taiwan.

出版信息

Cancer Med. 2023 Apr;12(8):9583-9588. doi: 10.1002/cam4.5734. Epub 2023 Feb 24.

Abstract

BACKGROUND

Certain angiotensin receptor blockers (ARBs) have peroxisome proliferator-activated receptor-γ (PPAR-γ) activation property, which has been associated with improved programmed cell death ligand 1 blockade and cytotoxic T lymphocyte-mediated antitumor activity.

METHODS

We conducted a retrospective cohort study to investigate the impact of PPAR-γ-activating ARBs on patient survival in patients treated with immune checkpoint inhibitors (ICIs) across all types of cancers.

RESULTS

A total of 167 patients receiving both angiotensin receptor blockers (ARBs) and immune checkpoint inhibitors (ICIs) were included. Compared with non-PPAR-γ-ARB users (n = 102), PPAR-γ-ARB users (n = 65) had a longer median overall survival (not reached [IQR, 16.0-not reached] vs. 18.6 [IQR, 6.1-38.6] months) and progression-free survival (17.3 [IQR, 5.1-not reached] vs. 8.2 [IQR, 2.4-18.6] months). In Cox regression analysis, the use of PPAR-γ-activating ARBs had an approximately 50% reduction in all-cause mortality and disease progression. Patients who received PPAR-γ-activating ARBs also had higher clinical benefit rates than non-PPAR-γ-ARB users (82% vs. 61%, p = 0.005).

CONCLUSION

The use of ARBs with PPAR-γ-activating property is linked with better survival among patients receiving ICIs.

摘要

背景

某些血管紧张素受体阻滞剂(ARBs)具有过氧化物酶体增殖物激活受体-γ(PPAR-γ)激活特性,这与程序性细胞死亡配体 1 阻断和细胞毒性 T 淋巴细胞介导的抗肿瘤活性的改善有关。

方法

我们进行了一项回顾性队列研究,以调查在接受免疫检查点抑制剂(ICI)治疗的所有类型癌症患者中,具有 PPAR-γ 激活作用的 ARBs 对患者生存的影响。

结果

共纳入 167 例同时接受血管紧张素受体阻滞剂(ARBs)和免疫检查点抑制剂(ICIs)治疗的患者。与非 PPAR-γ-ARB 使用者(n=102)相比,PPAR-γ-ARB 使用者(n=65)的中位总生存期更长(未达到[IQR,16.0-未达到]与 18.6 [IQR,6.1-38.6]个月)和无进展生存期更长(17.3 [IQR,5.1-未达到]与 8.2 [IQR,2.4-18.6]个月)。在 Cox 回归分析中,使用 PPAR-γ 激活型 ARBs 可使全因死亡率和疾病进展率降低约 50%。接受 PPAR-γ 激活型 ARBs 治疗的患者的临床获益率也高于非 PPAR-γ-ARB 使用者(82% vs. 61%,p=0.005)。

结论

在接受 ICI 治疗的患者中,使用具有 PPAR-γ 激活作用的 ARBs 与更好的生存相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ca1/10166924/615c16d35629/CAM4-12-9583-g002.jpg

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