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

Ionizing radiation sensitizes tumors to PD-L1 immune checkpoint blockade in orthotopic murine head and neck squamous cell carcinoma.

作者信息

Oweida Ayman, Lennon Shelby, Calame Dylan, Korpela Sean, Bhatia Shilpa, Sharma Jaspreet, Graham Caleb, Binder David, Serkova Natalie, Raben David, Heasley Lynn, Clambey Eric, Nemenoff Raphael, Karam Sana D

机构信息

Department of Radiation Oncology, University of Colorado Denver, Aurora, Colorado, USA.

Department of Craniofacial Biology, University of Colorado Denver, Aurora, Colorado, USA.

出版信息

Oncoimmunology. 2017 Aug 3;6(10):e1356153. doi: 10.1080/2162402X.2017.1356153. eCollection 2017.


DOI:10.1080/2162402X.2017.1356153
PMID:29123967
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5665079/
Abstract

Immunotherapy clinical trials targeting the programmed-death ligand axis (PD-1/PD-L1) show that most head and neck squamous cell carcinoma (HNSCC) patients are resistant to PD-1/PD-L1 inhibition. We investigated whether local radiation to the tumor can transform the immune landscape and render poorly immunogenic HNSCC tumors sensitive to PD-L1 inhibition. We used the first novel orthotopic model of HNSCC with genetically distinct murine cell lines. Tumors were resistant to PD-L1 checkpoint blockade, harbored minimal PD-L1 expression and tumor infiltrating lymphocytes at baseline, and were resistant to radiotherapy. The combination of radiation and PD-L1 inhibition significantly enhanced tumor control and improved survival. This was mediated in part through upregulation of PD-L1 on tumor cells and increased T-cell infiltration after RT, resulting in a highly inflamed tumor. Depletion of both CD4 and CD8 T-cells completely abrogated the effect of anti PD-L1 with radiation on tumor growth. Our findings provide evidence that radiation to the tumor can induce sensitivity to PD-L1 checkpoint blockade in orthotopic models of HNSCC. These findings have direct relevance to high risk HNSCC patients with poorly immunogenic tumors and who may benefit from combined radiation and checkpoint blockade.

摘要

相似文献

[1]
Ionizing radiation sensitizes tumors to PD-L1 immune checkpoint blockade in orthotopic murine head and neck squamous cell carcinoma.

Oncoimmunology. 2017-8-3

[2]
Resistance to Radiotherapy and PD-L1 Blockade Is Mediated by TIM-3 Upregulation and Regulatory T-Cell Infiltration.

Clin Cancer Res. 2018-7-24

[3]
The effect of Curcumin on multi-level immune checkpoint blockade and T cell dysfunction in head and neck cancer.

Phytomedicine. 2021-11

[4]
HPV16 E5 Mediates Resistance to PD-L1 Blockade and Can Be Targeted with Rimantadine in Head and Neck Cancer.

Cancer Res. 2019-12-17

[5]
The prognostic role of PD-L1 expression for survival in head and neck squamous cell carcinoma: A systematic review and meta-analysis.

Oral Oncol. 2018-9-17

[6]
Immune-checkpoint molecules on regulatory T-cells as a potential therapeutic target in head and neck squamous cell cancers.

Cancer Sci. 2020-5-19

[7]
PD-L1-positive circulating endothelial progenitor cells associated with immune response to PD-1 blockade in patients with head and neck squamous cell carcinoma.

Cancer Immunol Immunother. 2024-1-4

[8]
Current studies of immunotherapy in head and neck cancer.

Clin Otolaryngol. 2018-2

[9]
Current Understanding of the Mechanisms Underlying Immune Evasion From PD-1/PD-L1 Immune Checkpoint Blockade in Head and Neck Cancer.

Front Oncol. 2020-2-28

[10]
PD-L1-specific helper T-cells exhibit effective antitumor responses: new strategy of cancer immunotherapy targeting PD-L1 in head and neck squamous cell carcinoma.

J Transl Med. 2019-6-20

引用本文的文献

[1]
E5 Oncoprotein: A Key Player in Human Papillomavirus-Positive Head and Neck Cancer Pathogenesis and Therapy Resistance.

Viruses. 2025-4-1

[2]
Leveraging radiotherapy to improve immunotherapy outcomes: rationale, progress and research priorities.

Clin Transl Immunology. 2025-4-8

[3]
Impacts of combining PD-L1 inhibitor and radiotherapy on the tumour immune microenvironment in a mouse model of esophageal squamous cell carcinoma.

BMC Cancer. 2025-3-14

[4]
Atezolizumab following definitive chemoradiotherapy in patients with unresectable locally advanced esophageal squamous cell carcinoma - a multicenter phase 2 trial (EPOC1802).

Nat Cancer. 2025-3

[5]
Quantitative magnetic resonance imaging responses in head and neck cancer patients treated with magnetic resonance-guided hypofractionated radiation therapy.

Phys Imaging Radiat Oncol. 2025-1-2

[6]
Comparison of Antitumor Effects of Combinations of Immune Checkpoint Inhibitors With Dendritic Cells Intratumorally Injected into Irradiated Mouse Adenocarcinoma.

J Immunother. 2025-4-1

[7]
MHC class I upregulation contributes to the therapeutic response to radiotherapy in combination with anti-PD-L1/anti-TGF-β in squamous cell carcinomas with enhanced CD8 T cell memory-driven response.

Cancer Lett. 2025-1-1

[8]
Manipulating the EphB4-ephrinB2 axis to reduce metastasis in HNSCC.

Oncogene. 2025-2

[9]
Radiation drives tertiary lymphoid structures to reshape TME for synergized antitumour immunity.

Expert Rev Mol Med. 2024-10-23

[10]
Abscopal effect: from a rare phenomenon to a new frontier in cancer therapy.

Biomark Res. 2024-9-4

本文引用的文献

[1]
Distinct patterns of infiltrating CD8+ T cells in HPV+ and CD68 macrophages in HPV- oropharyngeal squamous cell carcinomas are associated with better clinical outcome but PD-L1 expression is not prognostic.

Oncotarget. 2017-2-28

[2]
Radiotherapy and immunotherapy: a beneficial liaison?

Nat Rev Clin Oncol. 2017-1-17

[3]
What does PD-L1 positive or negative mean?

J Exp Med. 2016-12-12

[4]
Suppression of Type I IFN Signaling in Tumors Mediates Resistance to Anti-PD-1 Treatment That Can Be Overcome by Radiotherapy.

Cancer Res. 2017-2-15

[5]
The head and neck cancer immune landscape and its immunotherapeutic implications.

JCI Insight. 2016-10-20

[6]
A hypofractionated radiation regimen avoids the lymphopenia associated with neoadjuvant chemoradiation therapy of borderline resectable and locally advanced pancreatic adenocarcinoma.

J Immunother Cancer. 2016-8-16

[7]
Antitumor Efficacy of Radiation plus Immunotherapy Depends upon Dendritic Cell Activation of Effector CD8+ T Cells.

Cancer Immunol Res. 2016-5-30

[8]
Current status and perspectives in translational biomarker research for PD-1/PD-L1 immune checkpoint blockade therapy.

J Hematol Oncol. 2016-5-27

[9]
The role of PD-L1 in the radiation response and clinical outcome for bladder cancer.

Sci Rep. 2016-1-25

[10]
Identification of the Cell-Intrinsic and -Extrinsic Pathways Downstream of EGFR and IFNγ That Induce PD-L1 Expression in Head and Neck Cancer.

Cancer Res. 2016-3-1

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