先进急诊医学

炎症细胞在慢性阻塞性肺疾病和肺癌免疫发病机制中作用的研究进展

陈 云波

右江民族医学院

罗 维贵

右江民族医学院附属医院

DOI: https://doi.org/10.59429/xjjz.v6i3.7292

Keywords: 慢性阻塞性肺疾病；肺癌；巨噬细胞；中性粒细胞；淋巴细胞；免疫机制

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Abstract

慢性阻塞性肺疾病（COPD）和肺癌是相关疾病，非小细胞肺癌的发病率和死亡风险都因COPD的存在而增加。 COPD 常伴有慢性病，在 COPD 众多慢性并发症中，肺癌是最重要的死亡原因之一。基因表达和遗传易感性、表观 遗传学、吸烟、上皮间充质转化、慢性炎症和氧化应激损伤等因素是这两种疾病的共同诱发因素。异常的炎症免疫 反应在这两种疾病的发生和发展中都起着作用。在免疫应答过程中，肿瘤微环境逐渐生成，有利于血管生成和免疫 抑制，最终由肿瘤细胞逃避免疫形成肿瘤。论文就 COPD 合并肺癌的异常免疫反应做一综述。

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References

[1] Zhou C, Qin Y, Zhao W, et al. International expert consensus on diagnosis and treatment of lung cancer complicated by chronic obstructive pulmonary disease[J]. Transl Lung Cancer Res,2023,12(8):1661-1701.

[2] Mark N M, Kargl J, Busch S E, et al. Chronic Obstructive Pulmonary Disease Alters Immune Cell Composition and Immune Checkpoint Inhibitor Efficacy in Non-Small Cell Lung Cancer[J]. Am J Respir Crit Care Med,2018,197(3):325-336.

[3] Meybodi S M, Farasati F B, Pourmolaei A, et al. Immune checkpoint inhibitors promising role in cancer therapy: clinical evidence and immune-related adverse events[J]. Med Oncol,2023,40(8):243.

[4] Sun F, Xiao Y, Shapiro S D, et al. Critical and distinct roles of cell typespecific NF-kappaB2 in lung cancer[J]. JCI Insight,2024,9(4):e164188.

[5] Liang Z W, Ge X X, Xu M D, et al. Tumor-associated macrophages promote the metastasis and growth of non-small-cell lung cancer cells through NF-kappaB/PP2Ac-positive feedback loop[J]. Cancer Sci,2021,112(6):2140-2157.

[6] Zhang L, Ludden C M, Cullen A J, et al. Nuclear factor kappa B expression in non-small cell lung cancer[J]. Biomed Pharmacother,2023(167):115459.

[7] Liu H, Yao M, Ren J. Codonopsis pilosula-derived glycopeptide dCP1 promotes the polarization of tumor-associated macrophage from M2-like to M1 phenotype[J]. Cancer Immunol Immunother,2024,73(7):128.

[8] Almatroodi S A, McDonald C F, Darby I A, et al. Characterization of M1/M2 Tumour-Associated Macrophages (TAMs) and Th1/Th2 Cytokine Profiles in Patients with NSCLC[J]. Cancer Microenviron,2016,9(1):1-11.

[9] Zheng X, Sarode P, Weigert A, et al. The HDAC2-SP1 Axis Orchestrates Protumor Macrophage Polarization[J]. Cancer Res,2023,83(14):2345-2357.

[10] Ma H, Zhang Z, Hu Q, et al. Shedding light on macrophage immunotherapy in lung cancer[J]. J Cancer Res Clin Oncol,2023,149(10):8143-8152.

[11] Gungabeesoon J, Gort-Freitas N A, Kiss M, et al. A neutrophil response linked to tumor control in immunotherapy[J]. Cell,2023,186(7):1448-1464. [12] Pfirschke C, Engblom C, Gungabeesoon J, et al. Tumor-Promoting Ly-6G(+) SiglecF(high) Cells Are Mature and Long-Lived Neutrophils[J]. Cell Rep,2020,32(12):108164.

[13] Sody S, Uddin M, Gruneboom A, et al. Distinct Spatio-Temporal Dynamics of Tumor-Associated Neutrophils in Small Tumor Lesions[J]. Front Immunol,2019(10):1419.

[14] Lei Q, Zhen S, Zhang L, et al. A2AR-mediated CXCL5 upregulation on macrophages promotes NSCLC progression via NETosis[J]. Cancer Immunol Immunother,2024,73(6):108.

[15] Kargl J, Zhu X, Zhang H, et al. Neutrophil content predicts lymphocyte depletion and anti-PD1 treatment failure in NSCLC[J]. JCI Insight,2019,4(24):e130850.

[16] Gentles A J, Newman A M, Liu C L, et al. The prognostic landscape of genes and infiltrating immune cells across human cancers[J]. Nat Med,2015,21(8):938-945.

[17] Armstrong A J, Geva R, Chung H C, et al. CXCR2 antagonist navarixin in combination with pembrolizumab in select advanced solid tumors: a phase 2 randomized trial[J]. Invest New Drugs,2024,42(1):145-159.

[18] Zhu L, Li X J, Gangadaran P, et al. Tumor-associated macrophages as a potential therapeutic target in thyroid cancers[J]. Cancer Immunol Immunother,2023,72(12):3895-3917.

[19] Hartupee C, Nagalo B M, Chabu C Y, et al. Pancreatic cancer tumor microenvironment is a major therapeutic barrier and target[J]. Front Immunol,2024(15):1287459.

[20] Hong X, Xiao Z. Changes in peripheral blood TBNK lymphocyte subsets and their association with acute exacerbation of chronic obstructive pulmonary disease[J]. J Int Med Res,2023,51(6):3000605231182556.

[21] Kim M S, Kim D S, Yuk H J, et al. Siraitia grosvenorii Extract Attenuates Airway Inflammation in a Murine Model of Chronic Obstructive Pulmonary Disease Induced by Cigarette Smoke and Lipopolysaccharide[J]. Nutrients,2023,15(2):468.

[22] Patel A J, Khan N, Richter A, et al. Deep immune B and plasma cell repertoire in non-small cell lung cancer[J]. Front Immunol,2023(14):1198665.

[23] Ang Z, Paruzzo L, Hayer K E, et al. Alternative splicing of its 5’-UTR limits CD20 mRNA translation and enables resistance to CD20-directed immunotherapies[J]. Blood,2023,142(20):1724-1739.

[24] Galasso L, Cerrito L, Maccauro V, et al. Hepatocellular Carcinoma and the Multifaceted Relationship with Its Microenvironment: Attacking the Hepatocellular Carcinoma Defensive Fortress[J]. Cancers (Basel),2024,16(10):1837.

[25] 李冯洋.外泌体介导miR-3473b靶向NF-κB对肺癌细胞肺内转移及B细胞数量的影响[J].实用癌症杂志,2023,38(6):871-875.

[26] Lin M, Huang Z, Chen Y, et al. Lung cancer patients with chronic obstructive pulmonary disease benefit from anti-PD-1/PD-L1 therapy[J]. Front Immunol,2022(13):1038715.

[27] Su S, Chen F, Lv X, et al. Predictive value of peripheral blood biomarkers in patients with non-small-cell lung cancer responding to anti-PD-1-based treatment[J]. Cancer Immunol Immunother,2024,73(1):12.

[28] Shang Q, Yu X, Sun Q, et al. Polysaccharides regulate Th1/Th2 balance: A new strategy for tumor immunotherapy[J]. Biomed Pharmacother,2024(170):115976.

[29] Thomas R, Qiao S, Yang X. Th17/Treg Imbalance: Implications in Lung Inflammatory Diseases[J]. Int J Mol Sci,2023,24(5):4865.

[30] 沙正凯.COPD合并肺癌患者的临床特征及辅助性T细胞水平与疾病发生的关系[D].新乡:新乡医学院,2019.

[31] Zhu J, Li Z, Chen J, et al. A comprehensive bioinformatics analysis of FOXP3 in nonsmall cell lung cancer[J]. Medicine (Baltimore),2022,101(50):e32102.

[32] Cui H, Wang N, Li H, et al. The dynamic shifts of IL-10-producing Th17 and IL-17-producing Treg in health and disease: a crosstalk between ancient “Yin-Yang” theory and modern immunology[J]. Cell Commun Signal, 2024,22(1):99.

[33] Chandnani N, Mandal A, Gupta I, et al. Association of WiskottAldrich syndrome protein (WASp) in epigenetic regulation of B cell differentiation in non-small-cell lung cancer (NSCLC)[J]. Med Oncol,2023,41(1):28.

[34] Mariniello A, Tabbo F, Indellicati D, et al. Comparing T Cell Subsets in Broncho-Alveolar Lavage (BAL) and Peripheral Blood in Patients with Advanced Lung Cancer[J]. Cells,2022,11(20):3226.

[35] Puyalto A, Rodriguez-Remirez M, Lopez I, et al. Trametinib sensitizes KRAS-mutant lung adenocarcinoma tumors to PD-1/PD-L1 axis blockade via Id1 downregulation[J]. Mol Cancer,2024,23(1):78.

[36] Biton J, Ouakrim H, Dechartres A, et al. Impaired TumorInfiltrating T Cells in Patients with Chronic Obstructive Pulmonary Disease Impact Lung Cancer Response to PD-1 Blockade[J]. Am J Respir Crit Care Med,2018,198(7):928-940.