首页|Remolding the tumor microenvironment by bacteria augments adoptive T cell therapy in advanced-stage solid tumors

Remolding the tumor microenvironment by bacteria augments adoptive T cell therapy in advanced-stage solid tumors

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The intricate tumor microenvironment presents formidable obstacles to the efficacy of adoptive T cell therapy in the management of solid tumors by limiting the infiltration and inducing exhaustion of the transferred T cells.Here,we developed a bacterial-based adjuvant approach that augments the efficacy of adoptive T-cell therapy for solid tumor treatment.Our study reveals that intratumor injection of E.coli MG1655 normalizes tumor vasculatures and reprograms tumor-associated macrophages into M1 phenotype that produce abundant CCL5,together facilitating tumor infiltration of adoptively transferred T cells.The depletion of tumor-associated macrophages or CCL5 neutralization in vivo leads to the significantly decreased solid tumor infiltration of adoptive T cells in the presence of bacteriotherapy.This combinatorial therapy,consisting of E.coli adjuvant and adoptive T-cell therapy,effectively eradicates early-stage melanoma and inhibits the progression of pancreatic tumors.Notably,this dual strategy also strengthened the distal tumor control capabilities of adoptive T-cell therapy through the induction of in situ tumor vaccination.This dual therapeutic approach involving bacterial therapy targeting the interior of solid tumors and adoptive T-cell therapy attacking the tumor periphery exhibits potent therapeutic efficacy in achieving the eradication of advanced-stage tumors,including melanoma and hepatocellular carcinoma,by converging attacks from both inside and outside the tumor tissues.

Chaojie Zhu、Chao Liu、Qing Wu、Tao Sheng、Ruyi Zhou、En Ren、Ruizhe Zhang、Zhengjie Zhao、Jiaqi Shi、Xinyuan Shen、Zhongquan Sun、Zhengwei Mao、Kaixin He、Lingxiao Zhang、Yuan Ding、Zhen Gu、Weilin Wang、Hongjun Li

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Department of Hepatobiliary and Pancreatic Surgery the Second Affiliated Hospital,School of Medicine,Zhejiang University,310009 Hangzhou,China

National Key Laboratory of Advanced Drug Delivery and Release Systems,College of Pharmaceutical Sciences,Zhejiang University,310058 Hangzhou,China

Liangzhu Laboratory,Zhejiang University Medical Center,311121 Hangzhou,China

State Key Laboratory of Stress Biology and Fujian Provincial Key Laboratory of Innovative Drug Target Research,School of Pharmaceutical Sciences,Xiamen University,361102 Xiamen,China

MOE Key Laboratory of Macromolecular Synthesis and Functionalization,Department of Polymer Science and Engineering,Zhejiang University,310027 Hangzhou,China

Interdisciplinary Nanoscience Center,Aarhus University,Aarhus C DK-8000,Denmark

Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang Province,310009 Hangzhou,China

ZJU-Pujian Research & Development Center of Medical Artificial Intelligence for Hepatobiliary and Pancreatic Disease,310058 Hangzhou,China

Jinhua Institute of Zhejiang University,321299 Jinhua,China

Department of General Surgery,Sir Run Run Shaw Hospital,School of Medicine,Zhejiang University,310016 Hangzhou,China

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2024

10.1038/s41392-024-02028-3

信号转导与靶向治疗(英文)

信号转导与靶向治疗(英文)

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ISSN：
年,卷(期)：2024.9(12)