调控固有免疫防治肺癌转移的研究进展

于盼; 姜怡; 阙祖俊; 罗斌; 田建辉

doi:10.3969/j.issn.1000-8179.2021.07.602

调控固有免疫防治肺癌转移的研究进展

doi: 10.3969/j.issn.1000-8179.2021.07.602

于盼^①,,
姜怡^①,
阙祖俊^②,
罗斌^①,
田建辉^{①, ②, ,}

①.
上海中医药大学附属龙华医院肿瘤科（上海市200032）
②.
上海市中医药研究院中医肿瘤研究所

基金项目:

国家自然科学基金项目 81973517

国家自然科学基金项目 81803777

国家自然科学基金项目 81703987

详细信息

作者简介:
于盼专业方向为中医药防治恶性肿瘤的临床与基础研究。E-mail：tcm_yp@163.com

通讯作者:
田建辉 tjhhawk@shutcm.edu.cn

计量
- 文章访问数: 206
- HTML全文浏览量: 7
- PDF下载量: 27
- 被引次数: 0
出版历程
- 收稿日期: 2020-12-06
- 刊出日期: 2021-04-15

Research progress of regulating innate immunity in prevention and treatment of lung cancer metastasis

Pan Yu^{①
,},
Yi Jiang^①,
Zujun Que^②,
Bin Luo^①,
Jianhui Tian^{①, ②
, ,}

①.
Department of Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
②.
Oncology Institute of Traditional Chinese Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai 200032, China

Funds:

the National Natural Science Foundation of China 81973517

the National Natural Science Foundation of China 81803777

the National Natural Science Foundation of China 81703987

More Information

Corresponding author: Jianhui Tian; E-mail: tjhhawk@shutcm.edu.cn

摘要

摘要: 远处转移是导致肺癌患者死亡的重要原因之一，肺癌转移的整体防控效率亟待提高。基于适应性免疫调控为主的免疫靶向治疗已经在晚期肺癌实现疗效的突破，充分证实了免疫编辑理论指导临床的重要价值，但对早期根治术后的远处转移的防治仍缺乏高水平临床证据，提示肺癌转移的发生有适应性免疫之外的机制。因此，本文聚焦探讨固有免疫紊乱与远处转移发生的关系，讨论了NK细胞、巨噬细胞、中性粒细胞、树突状细胞等固有免疫细胞与肿瘤细胞间的作用机制，调控固有免疫细胞防治肺癌转移的临床应用以及固有免疫细胞作为生物标志物丰富转移评估体系的价值。将固有免疫紊乱融合入肺癌转移的核心机制，创新提出“正虚伏毒”学说并构建转移特异性研究平台以探索免疫细胞间、免疫细胞与肿瘤细胞间的作用机制，寻找防治肺癌转移的关键靶点群，研发综合免疫疗法促进肺癌转移防控效率的提高。
- 肺癌 /
- 转移 /
- 固有免疫 /
- 正虚伏毒 /
- 免疫治疗
Abstract: Recurrence and metastasis are crucial clinical events leading to mortality in patients with lung cancer. The overall efficiency of prevention and control of lung cancer metastasis needs to be improved. The breakthrough in advanced lung cancer treatment achieved by immune-targeted therapy based on regulation of adaptive immunity fully confirms the clinical importance of immune editing in clinical guidance. However, there is still a lack of high-level clinical evidence for prevention and treatment of distant metastasis after early radical surgery, suggesting that lung cancer metastasis may have an alternative mechanism other than adaptive immunity. Therefore, this review focuses on the relationship between innate immune disorder and occurrence of distant metastasis. We further discuss the interaction between tumor cells and various innate immune cells such as NK cells, macrophages, neutrophils and dendritic cells, as well as the clinical applications of innate immune cell regulation in the prevention and treatment of lung cancer metastasis, including the role of innate immune cells as biomarkers to enrich the metastasis evaluation system. It links innate immune disorder to lung cancer metastasis and puts forward the theory of "hidden toxicity due to vital qi deficiency, " facilitating the establishment of a specific research platform to explore the interaction between immune cells and tumor cells for identifying key targets for the prevention and treatment of lung cancer metastasis and to develop comprehensive immunotherapy to improve the prevention and control efficiency of lung cancer metastasis.
- lung cancer /
- metastasis /
- innate immunity /
- hidden toxicity due to vital qi deficiency /
- immunotherapy

HTML全文

参考文献(40)

[1]	Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2020[J]. CA Cancer J Clin, 2020, 70(1): 7-30. doi: 10.3322/caac.21590
[2]	Stankovic B, Bjørhovde HAK, Skarshaug R, et al. Immune cell composition in human non- small cell lung cancer[J]. Front Immunol, 2018, 9: 3101-3121. http://www.researchgate.net/publication/330779953_Immune_Cell_Composition_in_Human_Non-small_Cell_Lung_Cancer/download
[3]	Charrier M, Mezquita L, Lueza B, et al. Circulating innate immune markers and outcomes in treatment-naïve advanced non-small cell lung cancer patients[J]. Eur J Cancer, 2019, 108: 88-96. doi: 10.1016/j.ejca.2018.12.017
[4]	da Costa Souza P, Parra ER, Atanazio MJ, et al. Different morphology, stage and treatment affect immune cell infiltration and longterm outcome in patients with non- small cell lung carcinoma[J]. Histopathology, 2012, 61(4): 587-596. doi: 10.1111/j.1365-2559.2012.04318.x
[5]	Milette S, Fiset PO, Walsh LA, et al. The innate immune architecture of lung tumors and its implication in disease progression[J]. J Pathol, 2019, 247(5): 589-605. doi: 10.1002/path.5241
[6]	Aktaş ON, Öztürk AB, Erman B, et al. Role of natural killer cells in lung cancer[J]. J Cancer Res Clin Oncol, 2018, 144(6): 997-1003. doi: 10.1007/s00432-018-2635-3
[7]	López-Soto A, Gonzalez S, Smyth MJ, et al. Control of metastasis by NK cells[J]. Cancer Cell, 2017, 32(2): 135-154. doi: 10.1016/j.ccell.2017.06.009
[8]	Fenerty KE, Padget M, Wolfson B, et al. Immunotherapy utilizing the combination of natural killer- and antibody dependent cellular cytotoxicity (Adcc)-mediating agents with poly (Adp-Ribose) polymerase (Parp) inhibition[J]. J Immunother Cancer, 2018, 6(1): 133-146. doi: 10.1186/s40425-018-0445-4
[9]	Prager I, Watzl C. Mechanisms of natural killer cell-mediated cellular cytotoxicity[J]. J Leukoc Biol, 2019, 105(6): 1319-1329. doi: 10.1002/JLB.MR0718-269R
[10]	Schmidt L, Eskiocak B, Kohn R, et al. Enhanced adaptive immune responses in lung adenocarcinoma through natural killer cell stimulation [J]. Proc Natl Acad Sci U S A, 2019, 116(35): 17460-17469. doi: 10.1073/pnas.1904253116
[11]	Chockley PJ, Chen J, Chen G, et al. Epithelial-mesenchymal transition leads to Nk cell-mediated metastasis-specific immunosurveillance in lung cancer[J]. J Clin Invest, 2018, 128(4): 1384-1396. doi: 10.1172/JCI97611
[12]	Mukaida N, Nosaka T, Nakamoto Y, et al. Lung macrophages: multifunctional regulator cells for metastatic cells[J]. Int J Mol Sci, 2018, 20 (1): 116-130. doi: 10.3390/ijms20010116
[13]	Chen M, Hu C, Gao Q, et al. Study on metastasis inhibition of kejinyan cecoction on lung cancer by affecting tumor microenvironment[J]. Cancer Cell Int, 2020, 20: 451-462. doi: 10.1186/s12935-020-01540-0
[14]	Wang Z, Zhao Y, Xu H, et al. Ctbp1 promotes tumour- associated macrophage infiltration and progression in non-small cell lung cancer [J]. J Cell Mol Med, 2020, 24(19): 11445-11456. doi: 10.1111/jcmm.15751
[15]	Hanna RN, Cekic C, Sag D, et al. Patrolling monocytes control tumor metastasis to the lung[J]. Science, 2015, 350(6263): 985-990. doi: 10.1126/science.aac9407
[16]	Narasimhan PB, Eggert T, Zhu YP, et al. Patrolling monocytes control Nk cell expression of activating and stimulatory receptors to curtail lung metastases[J]. J Immunol, 2020, 204(1): 192-198. doi: 10.4049/jimmunol.1900998
[17]	Li P, Lu M, Shi J, et al. Dual roles of neutrophils in metastatic colonization are governed by the host Nk cell status[J]. Nat Commun, 2020, 11(1): 4387-4400. doi: 10.1038/s41467-020-18125-0
[18]	Rayes RF, Mouhanna JG, Nicolau I, et al. Primary tumors induce neutrophil extracellular traps with targetable metastasis promoting effects [J]. JCI Insight, 2019, 4(16): 1-13. http://www.researchgate.net/publication/334693869_Primary_tumors_induce_neutrophil_extracellular_traps_with_targetable_metastasis_promoting_effects/download
[19]	Singhal S, Bhojnagarwala PS, O'Brien S, et al. Origin and role of a subset of tumor-associated neutrophils with antigen-presenting cell features in early-stage human lung cancer[J]. Cancer Cell, 2016, 30(1): 120-135. doi: 10.1016/j.ccell.2016.06.001
[20]	Zahran AM, Hetta HF, Mansour S, et al. Reviving up dendritic cells can run cancer immune wheel in non-small cell lung cancer: a prospective two-arm study[J]. Cancer Immunol Immunother, 2020. DOI: 10.1007/ s00262-00020-02704-00267.
[21]	Mohsenzadegan M, Peng RW, Roudi R. Dendritic cell/cytokine-induced killer cell-based immunotherapy in lung cancer: what we know and future landscape[J]. J Cell Physiol, 2020, 235(1): 74-86. doi: 10.1002/jcp.28977
[22]	Aller MA, Arias A, Arias JI, et al. Carcinogenesis: the cancer cell-mast cell connection[J]. Inflamm Res, 2019, 68(2): 103-116. doi: 10.1007/s00011-018-1201-4
[23]	Salamon P, Mekori YA, Shefler I. Lung cancer-derived extracellular vesicles: a possible mediator of mast cell activation in the tumor microenvironment[J]. Cancer Immunol Immunother, 2020, 69(3): 373-381. doi: 10.1007/s00262-019-02459-w
[24]	Godfrey DI, Le Nours J, Andrews DM, et al. Unconventional T cell targets for cancer immunotherapy[J]. Immunity, 2018, 48(3): 453-473. doi: 10.1016/j.immuni.2018.03.009
[25]	Moon EK. Γδt cells in lung cancer malignant pleural effusion: friend foe [J]? Am J Respir Cell Mol Biol, 2019, 61(2): 130-131. doi: 10.1165/rcmb.2019-0080ED
[26]	Koh J, Kim HY, Lee Y, et al. Il23-producing human lung cancer cells promote tumor growth via conversion of innate lymphoid cell 1 (Ilc1) into Ilc3[J]. Clin Cancer Res, 2019, 25(13): 4026-4037. doi: 10.1158/1078-0432.CCR-18-3458
[27]	ivori S, Pende D, Quatrini L, et al. Nk cells and Ilcs in tumor immunotherapy[J]. Mol Aspects Med, 2020. DOI: 10.1016/j.mam.2020.100870.
[28]	Di Vito C, Mikulak J, Zaghi E, et al. Nk cells to cure cancer[J]. Semin Immunol, 2019. DOI: 10.1016/j.smim.2019.1003.1004.
[29]	Wu SY, Fu T, Jiang YZ, et al. Natural killer cells in cancer biology and therapy[J]. Mol Cancer, 2020, 19(1): 120-145. doi: 10.1186/s12943-020-01238-x
[30]	Ichiki Y, Shigematsu Y, Baba T, et al. Development of adoptive immunotherapy with Kk-Lc-1-specific tcr-transduced Γδt cells against lung cancer cells[J]. Cancer Sci, 2020. DOI: 10.1111/cas.14612.
[31]	Sarode P, Zheng X, Giotopoulou GA, et al. Reprogramming of tumorassociated macrophages by targeting Β-catenin/Fosl2/arid5a signaling: a potential treatment of lung cancer[J]. Sci Adv, 2020. DOI: 10.1126/ sciadv.aaz6105.
[32]	Deligne C, Murdamoothoo D, Gammage AN, et al. Matrix-targeting immunotherapy controls tumor growth and spread by switching macrophage phenotype[J]. Cancer Immunol Res, 2020, 8(3): 368-382. doi: 10.1158/2326-6066.CIR-19-0276
[33]	Wang QT, Nie Y, Sun SN, et al. Tumor- associated antigen-based personalized dendritic cell vaccine in solid tumor patients[J]. Cancer Immunol Immunother, 2020, 69(7): 1375-1387. doi: 10.1007/s00262-020-02496-w
[34]	Choi MG, Kim YJ, Lee JC, et al. Efficacy of natural killer cell activity as a biomarker for predicting immunotherapy response in non-small cell lung cancer[J]. Thorac Cancer, 2020, 11(11): 3337-3345. doi: 10.1111/1759-7714.13677
[35]	Wisdom AJ, Hong CS, Lin AJ, et al. Neutrophils promote tumor resistance to radiation therapy[J]. Proc Natl Acad Sci U S A, 2019, 116(37): 18584-18589. doi: 10.1073/pnas.1901562116
[36]	Hu G, Wang S, Cheng P. Tumor-infiltrating tryptase(+) mast cells predict unfavorable clinical outcome in solid tumors[J]. Int J Cancer, 2018, 142 (4): 813-821. doi: 10.1002/ijc.31099
[37]	Lau CM, Adams NM, Geary CD, et al. Epigenetic control of innate and adaptive immune memory[J]. Nat Immunol, 2018, 19(9): 963-972. doi: 10.1038/s41590-018-0176-1
[38]	Myers JA, Miller JS. Exploring the Nk cell platform for cancer immunotherapy[J]. Nat Rev Clin Oncol, 2020. DOI: 10.1038/s41571-41020-40426-41577.
[39]	田建辉. "正虚伏毒"为肺癌发病的核心病机[J]. 上海中医药杂志, 2016, 50(12): 10-14. https://www.cnki.com.cn/Article/CJFDTOTAL-SHZZ201612003.htm
[40]	Que Z, Luo B, Zhou Z, et al. Establishment and characterization of a patient-derived circulating lung tumor cell line in vitro and in vivo[J]. Cancer Cell Int, 2019, 19: 21-34. doi: 10.1186/s12935-019-0735-z