文献检索文档翻译深度研究
Suppr Zotero 插件Zotero 插件
邀请有礼套餐&价格历史记录

新学期，新优惠

限时优惠:9月1日-9月22日

30天高级会员仅需29元

1天体验卡首发特惠仅需5.99元

了解详情
不再提醒
插件&应用
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
高级版
套餐订阅购买积分包
AI 工具
文献检索文档翻译深度研究
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2025

靶向 PARP11 以避免免疫抑制并改善实体瘤中的 CAR T 疗法。

Targeting PARP11 to avert immunosuppression and improve CAR T therapy in solid tumors.

机构信息

Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Institutes of Biology and Medical Sciences and Jiangsu Key Laboratory of Infection and Immunity, Soochow University, Suzhou, China.

出版信息

Nat Cancer. 2022 Jul;3(7):808-820. doi: 10.1038/s43018-022-00383-0. Epub 2022 May 30.

DOI:10.1038/s43018-022-00383-0
PMID:35637402
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9339499/
Abstract

Evasion of antitumor immunity and resistance to therapies in solid tumors are aided by an immunosuppressive tumor microenvironment (TME). We found that TME factors, such as regulatory T cells and adenosine, downregulated type I interferon receptor IFNAR1 on CD8 cytotoxic T lymphocytes (CTLs). These events relied upon poly-ADP ribose polymerase-11 (PARP11), which was induced in intratumoral CTLs and acted as a key regulator of the immunosuppressive TME. Ablation of PARP11 prevented loss of IFNAR1, increased CTL tumoricidal activity and inhibited tumor growth in an IFNAR1-dependent manner. Accordingly, genetic or pharmacologic inactivation of PARP11 augmented the therapeutic benefits of chimeric antigen receptor T cells. Chimeric antigen receptor CTLs engineered to inactivate PARP11 demonstrated a superior efficacy against solid tumors. These findings highlight the role of PARP11 in the immunosuppressive TME and provide a proof of principle for targeting this pathway to optimize immune therapies.

摘要

肿瘤微环境（TME）有助于肿瘤的抗肿瘤免疫逃逸和对治疗的耐药性。我们发现，TME 因子，如调节性 T 细胞和腺苷，下调了 CD8 细胞毒性 T 淋巴细胞（CTL）上的 I 型干扰素受体 IFNAR1。这些事件依赖于聚 ADP 核糖聚合酶 11（PARP11），PARP11 在肿瘤内 CTL 中被诱导，并作为免疫抑制性 TME 的关键调节剂。PARP11 的缺失可防止 IFNAR1 的丢失，增加 CTL 的肿瘤杀伤活性，并以 IFNAR1 依赖的方式抑制肿瘤生长。因此，PARP11 的遗传或药理学失活增强了嵌合抗原受体 T 细胞的治疗益处。PARP11 失活的嵌合抗原受体 CTL 对实体瘤显示出更好的疗效。这些发现强调了 PARP11 在免疫抑制性 TME 中的作用，并为靶向该途径以优化免疫治疗提供了原理证明。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8490/9339499/296b468f4d3f/nihms-1800982-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8490/9339499/78841b83b2cc/nihms-1800982-f0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8490/9339499/0de6df4d5d6a/nihms-1800982-f0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8490/9339499/a4652b88379b/nihms-1800982-f0010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8490/9339499/d51c5eedd1ef/nihms-1800982-f0011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8490/9339499/ad016e449e75/nihms-1800982-f0012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8490/9339499/08ea1d055742/nihms-1800982-f0013.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8490/9339499/74ccb8ead6b0/nihms-1800982-f0014.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8490/9339499/153717b9d9ab/nihms-1800982-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8490/9339499/52fe4019524c/nihms-1800982-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8490/9339499/d707e13e2a10/nihms-1800982-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8490/9339499/adeb8b39cd6c/nihms-1800982-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8490/9339499/ffc7e04c9f32/nihms-1800982-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8490/9339499/01b020260cc5/nihms-1800982-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8490/9339499/296b468f4d3f/nihms-1800982-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8490/9339499/78841b83b2cc/nihms-1800982-f0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8490/9339499/0de6df4d5d6a/nihms-1800982-f0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8490/9339499/a4652b88379b/nihms-1800982-f0010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8490/9339499/d51c5eedd1ef/nihms-1800982-f0011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8490/9339499/ad016e449e75/nihms-1800982-f0012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8490/9339499/08ea1d055742/nihms-1800982-f0013.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8490/9339499/74ccb8ead6b0/nihms-1800982-f0014.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8490/9339499/153717b9d9ab/nihms-1800982-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8490/9339499/52fe4019524c/nihms-1800982-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8490/9339499/d707e13e2a10/nihms-1800982-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8490/9339499/adeb8b39cd6c/nihms-1800982-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8490/9339499/ffc7e04c9f32/nihms-1800982-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8490/9339499/01b020260cc5/nihms-1800982-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8490/9339499/296b468f4d3f/nihms-1800982-f0007.jpg

相似文献

[1]
Targeting PARP11 to avert immunosuppression and improve CAR T therapy in solid tumors.

Nat Cancer. 2022-7

[2]
PARP11 inhibition inactivates tumor-infiltrating regulatory T cells and improves the efficacy of immunotherapies.

Cell Rep Med. 2024-7-16

[3]
Tumor Microenvironment Immunosuppression: A Roadblock to CAR T-Cell Advancement in Solid Tumors.

Cells. 2022-11-16

[4]
NK Cells Expressing a Chimeric Activating Receptor Eliminate MDSCs and Rescue Impaired CAR-T Cell Activity against Solid Tumors.

Cancer Immunol Res. 2019-1-16

[5]
ADP-ribosyltransferase PARP11 modulates the interferon antiviral response by mono-ADP-ribosylating the ubiquitin E3 ligase β-TrCP.

Nat Microbiol. 2019-4-15

[6]
Hurdles to breakthrough in CAR T cell therapy of solid tumors.

Stem Cell Res Ther. 2022-4-1

[7]
CAR-T Plus Radiotherapy: A Promising Combination for Immunosuppressive Tumors.

Front Immunol. 2021

[8]
Modulating tumor physical microenvironment for fueling CAR-T cell therapy.

Adv Drug Deliv Rev. 2022-6

[9]
Immunosuppression in tumor immune microenvironment and its optimization from CAR-T cell therapy.

Theranostics. 2022

[10]
Remodeling of Tumor Microenvironment by Tumor-Targeting Nanozymes Enhances Immune Activation of CAR T Cells for Combination Therapy.

Small. 2021-10

引用本文的文献

[1]
PARP (Poly ADP-ribose Polymerase) Family in Health and Disease.

MedComm (2020). 2025-9-1

[2]
Mono-ADP-ribosylating PARP enzymes in cellular signaling and disease.

J Cell Sci. 2025-7-15

[3]
Immunocytes in the tumor microenvironment: recent updates and interconnections.

Front Immunol. 2025-4-14

[4]
Expanding the horizon of CAR T cell therapy: from cancer treatment to autoimmune diseases and beyond.

Front Immunol. 2025-2-19

[5]
Tumor‑associated neutrophils: Critical regulators in cancer progression and therapeutic resistance (Review).

Int J Oncol. 2025-4

[6]
Exploration of the diagnostic and prognostic roles of decreased autoantibodies in lung cancer.

Front Immunol. 2025-1-30

[7]
PARP enzymes and mono-ADP-ribosylation: advancing the connection from interferon-signalling to cancer biology.

Expert Rev Mol Med. 2024-8-27

[8]
Modified C-type natriuretic peptide normalizes tumor vasculature, reinvigorates antitumor immunity, and improves solid tumor therapies.

Sci Transl Med. 2024-8-21

[9]
Pathological and physiological roles of ADP-ribosylation: established functions and new insights.

Biol Chem. 2024-7-29

[10]
Expanding the Perspective on PARP1 and Its Inhibitors in Cancer Therapy: From DNA Damage Repair to Immunomodulation.

Biomedicines. 2024-7-20

本文引用的文献

[1]
Antigen presentation in cancer: insights into tumour immunogenicity and immune evasion.

Nat Rev Cancer. 2021-5

[2]
Immune suppressive activity of myeloid-derived suppressor cells in cancer requires inactivation of the type I interferon pathway.

Nat Commun. 2021-3-19

[3]
Recent advances and discoveries in the mechanisms and functions of CAR T cells.

Nat Rev Cancer. 2021-3

[4]
Cancer-associated fibroblasts downregulate type I interferon receptor to stimulate intratumoral stromagenesis.

Oncogene. 2020-8-17

[5]
Oncolytic virus-derived type I interferon restricts CAR T cell therapy.

Nat Commun. 2020-6-24

[6]
Multi-phenotype CRISPR-Cas9 Screen Identifies p38 Kinase as a Target for Adoptive Immunotherapies.

Cancer Cell. 2020-6-8

[7]
The adenosine pathway in immuno-oncology.

Nat Rev Clin Oncol. 2020-10

[8]
PARP and PARG inhibitors in cancer treatment.

Genes Dev. 2020-2-6

[9]
Distinct epigenetic features of tumor-reactive CD8+ T cells in colorectal cancer patients revealed by genome-wide DNA methylation analysis.

Genome Biol. 2019-12-31

[10]
TOX transcriptionally and epigenetically programs CD8 T cell exhaustion.

Nature. 2019-6-17

文献AI研究员

20分钟写一篇综述，助力文献阅读效率提升50倍

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

推荐工具

医学文档翻译智能文献检索