药学学报, 2022, 57(2): 296-302
引用本文:
卜凡雪, 郑宇钊, 周建平*, 殷婷婕*. 基于活性氧的肿瘤免疫调控研究进展[J]. 药学学报, 2022, 57(2): 296-302.
BU Fan-xue, ZHENG Yu-zhao, ZHOU Jian-ping*, YIN Ting-jie*. Research process of reactive oxygen species-based tumor immunomodulation[J]. Acta Pharmaceutica Sinica, 2022, 57(2): 296-302.

基于活性氧的肿瘤免疫调控研究进展
卜凡雪, 郑宇钊, 周建平*, 殷婷婕*
中国药科大学药学院药剂系, 江苏 南京 211198
摘要:
活性氧(reactive oxygen species,ROS)是一类具有高反应活性、性质活泼的氧的电子还原产物,可维持机体正常生理功能和氧化还原稳态。肿瘤微环境中常处于氧化应激态,ROS可通过调节肿瘤细胞及多种免疫细胞的表型和功能影响肿瘤免疫应答的多个过程。随着免疫学的快速发展,基于ROS的肿瘤免疫调控被广泛关注与研究。本文从ROS的概念、产生和特性出发,对ROS参与肿瘤免疫应答的机制进行了总结,并对近年来基于ROS调控的策略在肿瘤免疫治疗领域的应用进行综述和分析。
关键词:    活性氧      氧化应激      免疫应答      肿瘤      免疫调控     
Research process of reactive oxygen species-based tumor immunomodulation
BU Fan-xue, ZHENG Yu-zhao, ZHOU Jian-ping*, YIN Ting-jie*
Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing 211198, China
Abstract:
Reactive oxygen species (ROS) is defined as the electron reduction product of oxygen with high reactivity which can maintain normal physiological functions and redox homeostasis. The tumor microenvironment is in a state of oxidative stress. ROS can affect multiple processes of tumor immune response by modulating the phenotype and functions of tumor cells and immune cells. With the rapid development of immunology, ROS-based tumor immunomodulation has been widely concerned and studied. In this review, the mechanism of ROS participating in tumor immune response is elaborated. Meanwhile, the research process and application of ROS in tumor immunomodulation in recent years are reviewed and analyzed.
Key words:    reactive oxygen species    oxidative stress    immune response    tumor    immunomodulation   
收稿日期: 2021-10-17
DOI: 10.16438/j.0513-4870.2021-1501
基金项目: 国家自然科学基金资助项目(81703442,81972835).
通讯作者: 周建平,Tel:86-25-83271102,E-mail:zhoujianp60@163.com;殷婷婕,E-mail:cookey_89ytj@163.com
Email: zhoujianp60@163.comcookey_89ytj@163.com
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参考文献:
[1] Galon J, Bruni D. Tumor immunology and tumor evolution:intertwined histories[J]. Immunity, 2020, 52:55-81.
[2] Robert C. A decade of immune-checkpoint inhibitors in cancer therapy[J]. Nat Commun, 2020, 11:3801.
[3] Augustin RC, Delgoffe GM, Najjar YG. Characteristics of the tumor microenvironment that influence immune cell functions:hypoxia, oxidative stress, metabolic alterations[J]. Cancers (Basel), 2020, 12:3802.
[4] Kotsafti A, Scarpa M, Castagliuolo I, et al. Reactive oxygen species and antitumor immunity-from surveillance to evasion[J]. Cancers (Basel), 2020, 12:1748.
[5] Mou Y, Wen S, Gao XX, et al. Advances in anti-tumor drug research based on reactive oxygen regulation[J]. Acta Pharm Sin (药学学报), 2020, 55:1453-1465.
[6] Zhou Z, Ni K, Deng H, et al. Dancing with reactive oxygen species generation and elimination in nanotheranostics for disease treatment[J]. Adv Drug Delivery Rev, 2020, 158:73-90.
[7] Huang MZ, Li JY. Physiological regulation of reactive oxygen species in organisms based on their physicochemical properties[J]. Acta Physiol, 2020, 228:e13351.
[8] Yang B, Chen Y, Shi J. Reactive oxygen species (ROS)-based nanomedicine[J]. Chem Rev, 2019, 119:4881-4985.
[9] Su LJ, Zhang JH, Gomez H, et al. Reactive oxygen species-induced lipid peroxidation in apoptosis, autophagy, and ferroptosis[J]. Oxid Med Cell Longev, 2019, 2019:5080843.
[10] Sarmiento-Salinas FL, Perez-Gonzalez A, Acosta-Casique A, et al. Reactive oxygen species:role in carcinogenesis, cancer cell signaling and tumor progression[J]. Life Sci, 2021, 284:119942.
[11] Phuengkham H, Ren L, Shin IW, et al. Nanoengineered immune niches for reprogramming the immunosuppressive tumor microenvironment and enhancing cancer immunotherapy[J]. Adv Mater, 2019, 31:e1803322.
[12] Vandenabeele P, Vandecasteele K, Bachert C, et al. Immunogenic apoptotic cell death and anticancer immunity[J]. Adv Exp Med Biol, 2016, 930:133-149.
[13] Guo J, Yu Z, Sun D, et al. Two nanoformulations induce reactive oxygen species and immunogenetic cell death for synergistic chemo-immunotherapy eradicating colorectal cancer and hepatocellular carcinoma[J]. Mol Cancer, 2021, 20:10.
[14] Krysko DV, Garg AD, Kaczmarek A, et al. Immunogenic cell death and DAMPs in cancer therapy[J]. Nat Rev Cancer, 2012, 12:860-875.
[15] Ho NI, Camps MG, Garcia-Vallejo JJ, et al. Distinct antigen uptake receptors route to the same storage compartments for cross-presentation in dendritic cells[J]. Immunology, 2021, 164:494-506.
[16] Wang C, Li P, Liu L, et al. Self-adjuvanted nanovaccine for cancer immunotherapy:role of lysosomal rupture-induced ROS in MHC class I antigen presentation[J]. Biomaterials, 2016, 79:88-100.
[17] Battisti F, Napoletano C, Rahimi Koshkaki H, et al. Tumor-derived microvesicles modulate antigen cross-processing via reactive oxygen species-mediated alkalinization of phagosomal compartment in dendritic cells[J]. Front Immunol, 2017, 8:1179.
[18] Mao D, Hu F, Yi Z, et al. AIEgen-coupled upconversion nanoparticles eradicate solid tumors through dual-mode ROS activation[J]. Sci Adv, 2020, 6:eabb2712.
[19] Chougnet CA, Thacker RI, Shehata HM, et al. Loss of phagocytic and antigen cross-presenting capacity in aging dendritic cells is associated with mitochondrial dysfunction[J]. J Immunol, 2015, 195:2624-2632.
[20] Chamoto K, Chowdhury PS, Kumar A, et al. Mitochondrial activation chemicals synergize with surface receptor PD-1 blockade for T cell-dependent antitumor activity[J]. Proc Natl Acad Sci U S A, 2017, 114:E761-E770.
[21] Sena LA, Li S, Jairaman A, et al. Mitochondria are required for antigen-specific T cell activation through reactive oxygen species signaling[J]. Immunity, 2013, 38:225-236.
[22] Tang L, Zheng Y, Melo MB, et al. Enhancing T cell therapy through TCR-signaling-responsive nanoparticle drug delivery[J]. Nat Biotechnol, 2018, 36:707-716.
[23] Deng H, Yang W, Zhou Z, et al. Targeted scavenging of extracellular ROS relieves suppressive immunogenic cell death[J]. Nat Commun, 2020, 11:4951.
[24] Feng YX, Mu RY, Wang ZZ, et al. A toll-like receptor agonist mimicking microbial signal to generate tumor-suppressive macrophages[J]. Nat Commun, 2019, 10:2272.
[25] Rong L, Zhang Y, Li WS, et al. Iron chelated melanin-like nanoparticles for tumor-associated macrophage repolarization and cancer therapy[J]. Biomaterials, 2019, 225:119515.
[26] Chen Q, Wang C, Zhang X, et al. In situ sprayed bioresponsive immunotherapeutic gel for post-surgical cancer treatment[J]. Nat Nanotechnol, 2019, 14:89-97.
[27] Xie R, Ruan S, Liu J, et al. Furin-instructed aggregated gold nanoparticles for re-educating tumor associated macrophages and overcoming breast cancer chemoresistance[J]. Biomaterials, 2021, 275:120891.
[28] Rodell CB, Arlauckas SP, Cuccarese MF, et al. TLR7/8-agonist-loaded nanoparticles promote the polarization of tumour-associated macrophages to enhance cancer immunotherapy[J]. Nat Biomed Eng, 2018, 2:578-588.
[29] Wei Z, Zhang X, Yong T, et al. Boosting anti-PD-1 therapy with metformin-loaded macrophage-derived microparticles[J]. Nat Commun, 2021, 12:440.
[30] Shi C, Liu T, Guo Z, et al. Reprogramming tumor-associated macrophages by nanoparticle-based reactive oxygen species photogeneration[J]. Nano Lett, 2018, 18:7330-7342.
[31] Liu L, He H, Liang R, et al. ROS-inducing micelles sensitize tumor-associated macrophages to TLR3 stimulation for potent immunotherapy[J]. Biomacromolecules, 2018, 19:2146-2155.
[32] Yang G, Ni JS, Li Y, et al. Acceptor engineering for optimized ROS generation facilitates reprogramming macrophages to M1 phenotype in photodynamic immunotherapy[J]. Angew Chem Int Ed Engl, 2021, 60:5386-5393.
[33] Roux C, Jafari SM, Shinde R, et al. Reactive oxygen species modulate macrophage immunosuppressive phenotype through the up-regulation of PD-L1[J]. Proc Natl Acad Sci U S A, 2019, 116:4326-4335.
[34] Murray PJ. Macrophage polarization[J]. Annu Rev Physiol, 2017, 79:541-566.
[35] Yunna C, Mengru H, Lei W, et al. Macrophage M1/M2 polarization[J]. Eur J Pharmacol, 2020, 877:173090.
[36] DeNardo DG, Ruffell B. Macrophages as regulators of tumour immunity and immunotherapy[J]. Nat Rev Immunol, 2019, 19:369-382.
[37] Liang W, He X, Bi J, et al. Role of reactive oxygen species in tumors based on the ‘seed and soil’ theory:a complex interaction[J]. Oncol Rep, 2021, 46:208.
[38] Maj T, Wang W, Crespo J, et al. Oxidative stress controls regula-tory T cell apoptosis and suppressor activity and PD-L1-blockade resistance in tumor[J]. Nat Immunol, 2017, 18:1332-1341.
[39] Jeong SD, Jung BK, Ahn HM, et al. Immunogenic cell death inducing fluorinated mitochondria-disrupting helical polypeptide synergizes with PD-L1 immune checkpoint blockade[J]. Adv Sci, 2021, 8:2001308.
[40] Wang L, Guan R, Xie L, et al. An ER-targeting iridium (III) complex that induces immunogenic cell death in non-small-cell lung cancer[J]. Angew Chem Int Ed Engl, 2021, 60:4657-4665.
[41] Li W, Yang J, Luo L, et al. Targeting photodynamic and photothermal therapy to the endoplasmic reticulum enhances immunogenic cancer cell death[J]. Nat Commun, 2019, 10:3349.
[42] Deng H, Zhou Z, Yang W, et al. Endoplasmic reticulum targeting to amplify immunogenic cell death for cancer immunotherapy[J]. Nano Lett, 2020, 20:1928-1933.
[43] Ji C, Si J, Xu Y, et al. Mitochondria-targeted and ultrasound-responsive nanoparticles for oxygen and nitric oxide codelivery to reverse immunosuppression and enhance sonodynamic therapy for immune activation[J]. Theranostics, 2021, 1:8587-8604.
[44] Tan X, Huang J, Wang Y, et al. Transformable nanosensitizer with tumor microenvironment-activated sonodynamic process and calcium release for enhanced cancer immunotherapy[J]. Angew Chem Int Ed Engl, 2021, 60:14051-14059.
[45] Yang J, Ma S, Xu R, et al. Smart biomimetic metal organic frameworks based on ROS-ferroptosis-glycolysis regulation for enhanced tumor chemo-immunotherapy[J]. J Control Release, 2021, 334:21-33.
[46] Wang H, Wang K, He L, et al. Engineering antigen as photo-sensitiser nanocarrier to facilitate ROS triggered immune cascade for photodynamic immunotherapy[J]. Biomaterials, 2020, 244:119964.
[47] Zhou Z, Wu H, Yang R, et al. GSH depletion liposome adjuvant for augmenting the photothermal immunotherapy of breast cancer[J]. Sci Adv, 2020, 6:eabc4373.
[48] Shao Y, Wang Z, Hao Y, et al. Cascade catalytic nanoplatform based on "butterfly effect" for enhanced immunotherapy[J]. Adv Healthc Mater, 2021, 10:e2002171.
[49] Ligtenberg MA, Mougiakakos D, Mukhopadhyay M, et al. Coexpressed catalase protects chimeric antigen receptor-redirected T cells as well as bystander cells from oxidative stress-induced loss of antitumor activity[J]. J Immunol, 2016, 196:759-766.
[50] Cen D, Ge Q, Xie C, et al. ZnS@BSA nanoclusters potentiate efficacy of cancer immunotherapy[J]. Adv Mater, 2021. DOI:10.1002/adma.202104037.
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