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利用固有 T 细胞靶向免疫抑制性肿瘤相关巨噬细胞以增强抗肿瘤反应性

英文原题:Targeting Immunosuppressive Tumor-Associated Macrophages Using Innate T Cells for Enhanced Antitumor Reactivity.

查看英文原题

Targeting Immunosuppressive Tumor-Associated Macrophages Using Innate T Cells for Enhanced Antitumor Reactivity.

PubMed 2022/06/01(内容时间) Cancers (Basel) Q2 · IF 4.8(JCR 2025)

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中文摘要

过去十年,基于 T 细胞和嵌合抗原受体(CAR)工程化 T(CAR-T)细胞的抗肿瘤免疫疗法取得显著发展;但移植物抗宿主病(GvHD)和肿瘤相关免疫抑制等问题仍是广泛采用和实施该疗法的重要障碍。近期先天免疫细胞 CAR 疗法的发展拓展了该疗法的应用空间,尤其有利于使用异体细胞来源及浸润实体瘤。本研究建立体外杀伤实验,评估 MAIT、iNKT 和 T 细胞靶向肿瘤相关巨噬细胞(TAM)的能力,并评估 CAR 工程化先天样 T 细胞的抗肿瘤能力及其用于临床治疗的潜力。体外结果显示,三种先天样 T 细胞均具有显著 TAM 杀伤能力,CAR 工程化先天样 T 细胞的抗肿瘤能力也得到增强。这些先天样 T 细胞可同时靶向肿瘤和 TAM,提示其有望用于抗肿瘤治疗,既增强细胞毒性,又改善肿瘤微环境(TME)免疫抑制。

展开英文摘要原文

The field of T cell-based and chimeric antigen receptor (CAR)-engineered T (CAR-T) cell-based antitumor immunotherapy has seen substantial developments in the past decade; however, considerable issues, such as graft-versus-host disease (GvHD) and tumor-associated immunosuppression, have proven to be substantial roadblocks to widespread adoption and implementation.

Recent developments in innate immune cell-based CAR therapy have opened several doors for the expansion of this therapy, especially as it relates to allogeneic cell sources and solid tumor infiltration.

This study establishes in vitro killing assays to examine the TAM-targeting efficacy of MAIT, iNKT, and T cells.

This study also assesses the antitumor ability of CAR-engineered innate T cells, evaluating their potential adoption for clinical therapies. The in vitro trials presented in this study demonstrate the considerable TAM-killing abilities of all three innate T cell types, and confirm the enhanced antitumor abilities of CAR-engineered innate T cells. The tumor- and TAM-targeting capacity of these innate T cells suggest their potential for antitumor therapy that supplements cytotoxicity with remediation of tumor microenvironment (TME)-immunosuppression.

论文信息

作者
Li YR、Brown J、Yu Y、Lee D、Zhou K、Dunn ZS、Hon R、Wilson M
单位
Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, CA 90095, USA.United States
期刊
Cancers2022 Jun 1
原文标识
PubMed 35681730 · DOI 10.3390/cancers14112749