De novo induction of intratumoral lymphoid structures and vessel normalization enhances immunotherapy in resistant tumors

被引：255

作者：

Johansson-Percival, Anna ^{[1
]}

He, Bo ^{[1
]}

Li, Zhi-Jie ^{[1
]}

Kjellen, Alva ^{[1
]}

Russell, Karen ^{[1
]}

Li, Ji ^{[1
]}

Larma, Irma ^{[2
]}

Ganss, Ruth ^{[1
]}

机构：

[1] Univ Western Australia, Harry Perkins Inst Med Res, Ctr Med Res, Nedlands, WA, Australia

[2] Univ Western Australia, Ctr Microscopy Characterizat & Anal, Crawley, WA, Australia

来源：

NATURE IMMUNOLOGY | 2017年 / 18卷 / 11期

基金：

英国医学研究理事会;

关键词：

T-CELL INFILTRATION; ESTABLISHED TUMORS; IMMUNE-RESPONSE; REGULATORY T; MICROENVIRONMENT; CANCER; DIFFERENTIATION; COMBINATION; DESTRUCTION; ERADICATION;

D O I：

10.1038/ni.3836

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

The tumor microenvironment confers profound resistance to anti-cancer immunotherapy. By targeting LIGHT, a member of the TNF superfamily of cytokines, to tumor vessels via a vascular targeting peptide (VTP), we developed a reagent with the dual ability to modulate the angiogenic vasculature and to induce tertiary lymphoid structures (TLSs). LIGHT-VTP triggered the influx of endogenous T cells into autochthonous or syngeneic tumors, which are resistant to immunotherapy. LIGHT-VTP in combination with checkpoint inhibition generated a large number of intratumoral effector and memory T cells with ensuing survival benefits, while the addition of anti-tumor vaccination achieved maximal therapeutic efficacy. Thus, the combination treatments stimulated the trafficking of pre-existing endogenous effector T cells as well as their intratumoral activation and were more successful than current immunotherapies, which fail due to tumor-intrinsic resistance mechanisms.

引用

页码：1207 / +

页数：16

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