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利用运动的免疫调节作用增强针对 B 细胞血液系统恶性肿瘤的单克隆抗体疗法疗效:一项叙述性综述

英文原题:Harnessing the immunomodulatory effects of exercise to enhance the efficacy of monoclonal antibody therapies against B-cell haematological cancers: a narrative review.

查看英文原题

Harnessing the immunomodulatory effects of exercise to enhance the efficacy of monoclonal antibody therapies against B-cell haematological cancers: a narrative review.

PubMed 2023/08/23(内容时间) Front Oncol Q2 · IF 3.4(JCR 2025)

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中文摘要

治疗性单克隆抗体(mAbs)是许多B细胞血液系统恶性肿瘤的标准治疗。这些mAbs的作用机制包括:通过激活固有免疫细胞上的Fcγ受体诱导癌细胞裂解;调理靶细胞以进行抗体依赖性细胞毒性或吞噬作用,和/或触发经典补体途径;同时结合癌细胞与T细胞以形成免疫突触并激活穿孔素介导的T细胞对癌细胞的细胞毒性;阻断免疫检查点以促进T细胞对免疫原性癌细胞克隆的细胞毒性;以及通过靶细胞对mAbs的内化直接递送细胞毒性药物。虽然包含mAb治疗的方案可以导致持久的抗癌反应,但由于mAb治疗未能根除微小残留病,疾病复发很常见。限制mAb疗效的因素包括:效应细胞频率不理想、明显的免疫耗竭和/或免疫无反应性,以及弥漫性扩散的肿瘤细胞在不同基质微环境中的存活。在这篇综述中,我们讨论由结构化急性运动暴露引起的免疫调节变化如何通过增强(i)抗体依赖性细胞毒性、(ii)抗体依赖性细胞吞噬作用、(iii)补体依赖性细胞毒性、(iv)T细胞细胞毒性,以及(v)细胞毒性药物的直接递送来改善mAb治疗疗效。

展开英文摘要原文

Therapeutic monoclonal antibodies (mAbs) are standard care for many B-cell haematological cancers. The modes of action for these mAbs include: induction of cancer cell lysis by activating Fcγ-receptors on innate immune cells; opsonising target cells for antibody-dependent cellular cytotoxicity or phagocytosis, and/or triggering the classical complement pathway; the simultaneous binding of cancer cells with T-cells to create an immune synapse and activate perforin-mediated T-cell cytotoxicity against cancer cells; blockade of immune checkpoints to facilitate T-cell cytotoxicity against immunogenic cancer cell clones; and direct delivery of cytotoxic agents via internalisation of mAbs by target cells.

While treatment regimens comprising mAb therapy can lead to durable anti-cancer responses, disease relapse is common due to failure of mAb therapy to eradicate minimal residual disease. Factors that limit mAb efficacy include: suboptimal effector cell frequencies, overt immune exhaustion and/or immune anergy, and survival of diffusely spread tumour cells in different stromal niches.

In this review, we discuss how immunomodulatory changes arising from exposure to structured bouts of acute exercise might improve mAb treatment efficacy by augmenting (i) antibody-dependent cellular cytotoxicity, (ii) antibody-dependent cellular phagocytosis, (iii) complement-dependent cytotoxicity, (iv) T-cell cytotoxicity, and (v) direct delivery of cytotoxic agents.

论文信息

作者
Collier-Bain HD、Brown FF、Causer AJ、Emery A、Oliver R、Moore S、Murray J、Turner JE
单位
Department for Health, University of Bath, Bath, United Kingdom.United Kingdom
文献类型
综述
期刊
Frontiers in oncology2023
原文标识
PubMed 37681023 · DOI 10.3389/fonc.2023.1244090