Role of neutrophils and NETs in osteosarcoma and soft tissue sarcoma

doi:10.16352/j.issn.1001-6325.2024.10.1442

Abstract

Abstract: Neutrophils are one of the important components of the tumor microenvironment. Neutrophil extra cellular traps (NETs) are a network structure released by neutrophils, and their formation process is called neutrophil inflammatory apoptosis (NETosis). Neutrophils in the tumor microenvironment, also known as tumor associated neutrophils (TANs). TANs including N1 phenotype and N2 phenotype have a bidirectional regulatory effect on tumors. While N1 phenotype inhibits tumor growth, and N2 phenotype promotes tumor growth, and N1 and N2 types undergo mutual transformation due to the influence of the tumor microenvironment. Neutrophils and NETs also play important roles in bone and osteosarcoma tissue sarcoma, which can affect tumor progression and predict patient prognosis. Blocking the formation of NETs may be a potential therapeutic target.

Key words: osteosarcoma, soft tissue sarcoma, neutrophil, neutrophil extracellular traps, tumor-associated neutrophils

CLC Number:

R738.6

References

[1]Thiam HR, Wong SL, Qiu R, et al. NETosis proceeds by cytoskeleton and endomembrane disassembly and PAD4-mediated chromatin decondensation and nuclear envelope rupture[J]. Proc Natl Acad Sci USA, 2020, 117: 7326-7337.
[2]Yapar A, Ali Tokgöz M, Yapar D, et al. Diagnostic and prognostic role of neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, and lymphocyte/monocyte ratio in patients with osteosarcoma[J]. Jt Dis Relat Surg, 2021, 32: 489-496.
[3]Huang X, Liu Y, Liang W, et al. A new model of preoperative systemic inflammatory markers predicting overall survival of osteosarcoma: a multicenter retrospective study[J]. BMC Cancer, 2022, 22: 1370. doi: 10.1186/s12885-022-10477-8.
[4]叶尔哈那提·胡杜斯, 阿尔恒别克·吐汗拜, 艾克拜尔·尤努斯. NLR、LMR和PLR与骨肉瘤预后的关系[J]. 肿瘤防治研究, 2021, 48: 381-386.
[5]Huang X, Liu Y, Liang W, et al. The combination of baseline neutrophil to lymphocyte ratio and dynamic changes during treatment can better predict the survival of osteosarcoma patients[J]. BMC Cancer, 2022, 22: 1370. doi: 10.3389/fonc.2023.1235158.
[6]邓欢, 曹博, 崔昊, 等. 中性粒细胞和淋巴细胞之比与腹膜后脂肪肉瘤术后复发的相关性[J]. 中华实验外科杂志, 2021, 38: 2243-2246.
[7]Awaji K, Miyagawa T, Omatsu J, et al. Prognostic relevance of pretreatment peripheral neutrophil count and neutrophil-to-lymphocyte ratio in primary cutaneous angiosarcoma[J]. Acta Derm-Venereol, 2021, 101: adv00527. doi: 10.2340/00015555-3898.
[8]García-Ortega DY, Melendez-Fernandez AP, Alvarez-Cano A, et al. Neutrophil-to-lymphocyte ratio as a prognostic biomarker in extremities undifferentiated pleomorphic sarcoma[J]. Surg Oncol, 2022, 42: 101746. doi: 10.1016/j.suronc.2022.101746.
[9]Tepper SC, Lee L, Fice MP, et al. Association between neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, and survival in undifferentiated pleomorphic sarcoma (NLR, PLR, and overall survival in UPS)[J]. Surg Oncol, 2023, 49: 101949. doi: 10.1016/j.suronc.2023.101949.
[10]Griffiths TT. The baseline neutrophil lymphocyte ratio predicts survival in soft-tissue sarcoma: a 17-year cohort study[J]. J Plast Reconstr Aesthet Surg, 2022,75:1372-1379. doi: 10.1016/j.bjps.2021.11.063.
[11]Sato Y, Nakano K, Wang X, et al. Pre-treatment neutrophil-to-lymphocyte ratio (NLR) as a predictive marker of pazopanib treatment for soft-tissue sarcoma[J]. Cancers, 2021, 13: 6266. doi: 10.3390/cancers13246266.
[12]Sato Y, Nakano K, Kawaguchi K, et al. Changes in neutrophil-to-lymphocyte ratio predict efficacy of trabectedin for soft-tissue sarcoma[J]. Cancer Diagn Progn, 2021, 1: 303-308. doi: 10.21873/cdp.10040.
[13]Sato Y, Nakano K, Fukuda N, et al. Pre-treatment neutrophil-to-lymphocyte ratio predicts efficacy of eribulin for soft-tissue sarcoma[J]. Anticancer Res, 2021, 41: 527-532. doi: 10.21873/anticanres.14804.
[14]Yamamoto H, Namba K, Yamamoto H, et al. The neutrophil-to-lymphocyte ratio as a novel independent prognostic factor for multiple metastatic lung tumors from various sarcomas[J]. Surg Today, 2021, 51: 127-135. doi: 10.1007/s00595-020-02093-5.
[15]Ponzetta A, Carriero R, Carnevale S, et al. Neutrophils driving unconventional T cells mediate resistance against murine sarcomas and selected human tumors[J]. Cell, 2019, 178: 346-360.e24. doi: 10.1016/j.cell.2019.05.047.
[16]Wang J, Gong M, Xiong Z, et al. Immune-related prognostic genes signatures in the tumor microenvironment of sarcoma[J]. Math Biosci Eng, 2021, 18: 2243-2257. doi: 10.3934/mbe.2021113.
[17]Bal O, Acikgoz Y, Yildiz B, et al. Simple and easily accessible prognostic markers in ewing sarcoma; neutrophil-lymphocyte ratio, neutrophil-platelet score and systemic-inflammation index[J]. J Cancer Res Ther, 2023, 19: 1241-1247. doi: 10.4103/jcrt.jcrt_1741_21.
[18]Stahl D, Gentles AJ, Thiele R, et al. Prognostic profiling of the immune cell microenvironment in Ewing's sarcoma family of tumors[J]. Oncoimmunology, 2019, 8: e1674113. doi: 10.1080/2162402X.2019.1674113.
[19]张海灵, 杨玉, 周倩倩, 等. 微囊藻毒素-LR 处理的中性粒细胞 NETs 促进结直肠癌细胞迁移[J]. 基础医学与临床, 2023, 43: 967-973.
[20]Yang L, Liu Q, Zhang X, et al. DNA of neutrophil extracellular traps promotes cancer metastasis via CCDC25[J]. Nature, 2020, 583: 133-138. doi: 10.1038/s41586-020-2394-6.
[21]Leshner M, Wang S, Lewis C, et al. PAD4 mediated histone hypercitrullination induces heterochromatin decondensation and chromatin unfolding to form neutrophil extracellular trap-like structures[J]. Front Immunol, 2012, 3: 307. doi: 10.3389/fimmu.2012.00307.
[22]Lin Y, Tang H, Teng H, et al. Development and validation of neutrophil extracellular traps-derived signature to predict the prognosis for osteosarcoma patients[J]. Int Immunopharmacol, 2024, 127: 111364. doi: 10.1016/j.intimp.2023.111364.
[23]Zhu D, Lu Y, Hu B, et al. Highly-tumor-targeted PAD4 inhibitors with PBA modification inhibit tumors in vivo by specifically inhibiting the PAD4-H3cit-NETs pathway in neutrophils[J]. Eur J Med Chem, 2023, 258: 115619. doi: 10.1016/j.ejmech.2023.115619.
[24]Liu B, He S, Li C, et al. Development of a prognostic neutrophil extracellular traps related lncRNA signature for soft tissue sarcoma using machine learning[J]. Front Immunol, 2024, 14: 1321616. doi: 10.3389/fimmu.2023.1321616.
[25]Shukrun R, Baron S, Fidel V, et al. Suggested role for neutrophil extracellular trap formation in Ewing sarcoma immune microenvironment[J]. Cancer Sci, 2023: cas.15992. doi: 10.1111/cas.15992.