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癌症免疫疗法与放疗和/或化疗联合应用:作用机制与临床治疗

Cancer Immunotherapy in Combination with Radiotherapy and/or Chemotherapy: Mechanisms and Clinical Therapy.

作者信息

Wang Xinmin, Jing Jing

机构信息

Institute of Breast Health Medicine West China Hospital, Sichuan University Chengdu Chengdu Sichuan China.

Department of General Surgery West China Hospital, Sichuan University Chengdu Sichuan China.

出版信息

MedComm (2020). 2025 Aug 31;6(9):e70346. doi: 10.1002/mco2.70346. eCollection 2025 Sep.


DOI:10.1002/mco2.70346
PMID:40900811
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12399610/
Abstract

Since the United States Food and Drug Administration approved the first immune checkpoint inhibitor ipilimumab for metastatic melanoma in 2011, ICIs have been approved for a range of cancers and significantly improving treatment outcomes. However, the objective response rate of ICI monotherapy remains modest (10-40%), with clinical benefit observed in only 15-20% of patients. The limited efficacy of ICIs in many patients is often attributed to poorly immunogenic ("cold") tumors. Radiotherapy and chemotherapy exhibit immunomodulatory properties that can enhance tumor immunogenicity. These effects provide a rationale for combining ICIs with conventional therapies. Current research lacks systematic synthesis and consistent clinical evidence on the immunomodulatory effects of radio/chemotherapy, and the optimal selection and sequencing of radio/chemotherapy with immunotherapy remain unclear, limiting the optimization of combination strategies with immunotherapy. This review outlines the current landscape of cancer immunotherapy and elucidates the immunomodulatory effects of radiotherapy and chemotherapy that form the basis for combination strategies. It further summarizes clinical advances in combined modalities and discusses associated toxicities, management approaches, and potential predictive biomarkers. This review provides a comprehensive framework for understanding and optimizing radio/chemo-immunotherapy by integrating mechanistic insights with clinical evidence to guide future personalized cancer treatment strategies.

摘要

自2011年美国食品药品监督管理局批准首款免疫检查点抑制剂伊匹单抗用于治疗转移性黑色素瘤以来,免疫检查点抑制剂已被批准用于多种癌症,并显著改善了治疗效果。然而,免疫检查点抑制剂单药治疗的客观缓解率仍然不高(10%-40%),仅15%-20%的患者观察到临床获益。免疫检查点抑制剂在许多患者中疗效有限,这通常归因于免疫原性较差的(“冷”)肿瘤。放疗和化疗具有免疫调节特性,可增强肿瘤免疫原性。这些效应为免疫检查点抑制剂与传统疗法联合应用提供了理论依据。目前的研究缺乏关于放疗/化疗免疫调节作用的系统综合和一致的临床证据,放疗/化疗与免疫治疗的最佳选择和顺序仍不明确,限制了免疫治疗联合策略的优化。本综述概述了癌症免疫治疗的现状,阐明了放疗和化疗的免疫调节作用,这些作用构成了联合策略的基础。它进一步总结了联合治疗模式的临床进展,并讨论了相关毒性、管理方法和潜在的预测生物标志物。本综述通过将机制见解与临床证据相结合,为理解和优化放疗/化疗-免疫治疗提供了一个全面的框架,以指导未来的个性化癌症治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a14/12399610/2d1edb8ddd7f/MCO2-6-e70346-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a14/12399610/33130b017bfc/MCO2-6-e70346-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a14/12399610/b62b0dd66bff/MCO2-6-e70346-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a14/12399610/dc733acc1af1/MCO2-6-e70346-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a14/12399610/2d1edb8ddd7f/MCO2-6-e70346-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a14/12399610/33130b017bfc/MCO2-6-e70346-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a14/12399610/b62b0dd66bff/MCO2-6-e70346-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a14/12399610/dc733acc1af1/MCO2-6-e70346-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a14/12399610/2d1edb8ddd7f/MCO2-6-e70346-g005.jpg

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本文引用的文献

[1]
Characteristics of relapsed/refractory diffuse large B-cell lymphoma patients with durable responses to maveropepimut-S, pembrolizumab, and cyclophosphamide: Long-term follow-up from the SPiReL trial.

EJHaem. 2024-12-12

[2]
A STING agonist prodrug reprograms tumor-associated macrophage to boost colorectal cancer immunotherapy.

Theranostics. 2025-1-1

[3]
HO-1 impairs the efficacy of radiotherapy by redistributing cGAS and STING in tumors.

J Clin Invest. 2024-12-2

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Nat Med. 2024-12

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J Clin Invest. 2024-12-2

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Pharmacol Res. 2024-10

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JAMA Oncol. 2024-9-1

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Inflamm Res. 2024-9

[10]
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Lancet Gastroenterol Hepatol. 2024-8

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