Facilitating T Cell Infiltration in Tumor Microenvironment Overcomes Resistance to PD-L1 Blockade

Tang Haidong; Wang Yang; Chlewicki Lukasz K.; Zhang Yuan; Guo Jingya; Liang Wei; Wang Jieyi; Wang Xiaoxiao; Fu Yang-Xin

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Facilitating T Cell Infiltration in Tumor Microenvironment Overcomes Resistance to PD-L1 Blockade

机译：促进肿瘤微环境中的T细胞浸润克服了对PD-L1封闭的抗性

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Immune checkpoint blockade therapies fail to induce responses in the majority of cancer patients, so how to increase the objective response rate becomes an urgent challenge. Here, we demonstrate that sufficient T cell infiltration in tumor tissues is a prerequisite for response to PD-L1 blockade. Targeting tumors with tumor necrosis factor superfamily member LIGHT activates lymphotoxin beta-receptor signaling, leading to the production of chemokines that recruit massive numbers of T cells. Furthermore, targeting non-T cell-inflamed tumor tissues by antibody-guided LIGHT creates a T cell-inflamed microenvironment and overcomes tumor resistance to checkpoint blockade. Our data indicate that targeting LIGHT might be a potent strategy to increase the responses to checkpoint blockades and other immunotherapies in non-T cell-inflamed tumors.

机译：免疫检查点阻断疗法未能在大多数癌症患者中诱导反应，因此如何增加客观反应率成为紧急挑战。在这里，我们证明肿瘤组织中足够的T细胞浸润是对PD-L1阻断的前提。靶向肿瘤坏死因子超家族成员光激活淋巴毒素β受体信号传导，导致越周的趋化因子的产生。此外，通过抗体引导光靶向非T细胞发炎的肿瘤组织产生T细胞发炎的微环境，并克服肿瘤抵抗检查点延迟。我们的数据表明，靶向光可能是一种有效的策略，以增加对非T细胞发炎的肿瘤中的检查点梗阻和其他免疫检查的反应。

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《Cancer Cell》 |2016年第3期|共12页
作者
Tang Haidong; Wang Yang; Chlewicki Lukasz K.; Zhang Yuan; Guo Jingya; Liang Wei; Wang Jieyi; Wang Xiaoxiao; Fu Yang-Xin;
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作者单位

Univ Chicago Dept Pathol 5841 S Maryland Ave Chicago IL 60637 USA;

Univ Chicago Dept Pathol 5841 S Maryland Ave Chicago IL 60637 USA;

Univ Chicago Dept Pathol 5841 S Maryland Ave Chicago IL 60637 USA;

Univ Chicago Dept Pathol 5841 S Maryland Ave Chicago IL 60637 USA;

Chinese Acad Sci Key Lab Infect &

Immun IBP UTSW Joint Immunotherapy Grp Inst Biophys Beijing;

Chinese Acad Sci Key Lab Infect &

Immun IBP UTSW Joint Immunotherapy Grp Inst Biophys Beijing;

AbbVie Biotherapeut Res ABR Oncol Biol 1500 Seaport Blvd Redwood City CA 94063 USA;

Alphamab Co Ltd Suzhou 215125 Jiangsu Peoples R China;

Univ Texas SW Med Ctr Dallas Dept Pathol Dallas TX 75235 USA;

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原文格式 PDF
正文语种 eng
中图分类肿瘤学;
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专利

1. Facilitating T Cell Infiltration in Tumor Microenvironment Overcomes Resistance to PD-L1 Blockade (vol 29, pg 285, 2016) [J] . Tang Haidong, Wang Yang, Chlewicki Lukasz K., Cancer Cell . 2016,第3期

机译：在肿瘤微环境中促进T细胞浸润克服了对PD-L1阻滞的抵抗力（第29卷，第285页，2016）
2. PD-1/PD-L1 Blockade Together With Vaccine Therapy Facilitates Effector T-Cell Infiltration Into Pancreatic Tumors [J] . Soares Kevin C., Rucki Agnieszka A., Wu Annie A., Journal of immunotherapy . 2015,第1期

机译：PD-1 / PD-L1阻断与疫苗治疗一起促进效应T细胞渗透入胰腺肿瘤
3. Variable density of CD8+ and CD25+ programmed cell death-1 (PD-1) ligand (PD-L1) CD4+ T cells within the tumor microenvironment causes differential responses to the PD-1/PD-L1 blockade [J] . Si-Pei Wu, Yi-Long Wu Journal for ImmunoTherapy of Cancer . 2015,第S2期

机译：肿瘤微环境中CD8 +和CD25 +程序性细胞死亡1（PD-1）配体（PD-L1）CD4 + T细胞的可变密度导致对PD-1 / PD-L1封锁的不同反应
4. Modulation of Intracellular Ceramide using Polymeric Nanoparticles to Overcome Multidrug Resistance in Tumor Cells [C] . L.E. van Vlerken, D. Shenoy, Z. Duan, Nano Science and Technology Institute(NSTI) Nanotechnology Conference and Trade Show(NSTI Nanotech 2006) vol.2 . 2006

机译：调节细胞内神经酰胺，使用聚合物纳米颗粒克服肿瘤细胞的多药耐药性
5. Super-charged NK cells increase immune infiltration in the tumor microenvironment and inhibit tumor growth in humanized-BLT mice. [D] . Kaur, Kawaljit. 2017

机译：荷电的NK细胞增加了肿瘤微环境中的免疫浸润，并抑制了人源化BLT小鼠的肿瘤生长。
6. Facilitating T cell infiltration in tumor microenvironment overcomes resistance to PD-L1 blockade [O] . Haidong Tang, Yang Wang, Lukasz K Chlewicki, -1

机译：促进肿瘤微环境中的T细胞浸润克服了对PD-L1阻滞的抵抗力
7. Facilitating T Cell Infiltration in Tumor Microenvironment Overcomes Resistance to PD-L1 Blockade [O] . Haidong Tang, Yang Wang, Lukasz K. Chlewicki, 2016

机译：促进肿瘤微环境中的T细胞浸润克服了对PD-L1封闭的抗性

Facilitating T Cell Infiltration in Tumor Microenvironment Overcomes Resistance to PD-L1 Blockade

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