MDSCs在消化系统肿瘤中的作用及其靶向治疗的研究进展
The Role of MDSCs in Digestive System Tumors and Research Progress in Targeted Therapy
DOI: 10.12677/acm.2024.1492548, PDF,    科研立项经费支持
作者: 黄丽葶*：桂平市人民医院遗传实验室，广西 桂平；刘姗姗#：桂林医学院附属医院检验科，广西 桂林
关键词: 髓源抑制性细胞(MDSCs)；消化系统肿瘤；肿瘤微环境；靶向治疗；Myeloid-Derived Suppressor Cells (MDSCs)； Digestive System Tumors； Tumor Microenvironment； Targeted Therapy
摘要: 消化系统肿瘤在我国的发病率高且存活率低，尽管随着医学的不断发展，目前的治疗手段能够在一定程度上提高和改善患者的生存率及预后，但总的生存率仍没有达到人们预期。肿瘤微环境(TME)由多种免疫细胞组成，其中髓源抑制细胞(MDSCs)是起免疫抑制作用的重要组成部分，它通过抑制机体的免疫细胞如T细胞或者自然杀伤细胞(NK细胞)来帮助肿瘤细胞发生免疫逃逸。研究发现MDSCs的生成、分化、数量及凋亡与消化系统肿瘤的发生发展密切相关，并且靶向MDSCs可作为消化系统肿瘤靶向治疗的潜在靶点，因此本文就MDSCs在消化系统肿瘤中的作用及其靶向治疗的研究做一综述。
Abstract: The incidence rate of digestive system tumors in China is high and the survival rate is low. With the continuous development of medicine, the current treatment methods can improve the survival rate and prognosis of patients, but the overall survival rate still does not meet patient expected. The tumor microenvironment (TME) is composed of various immune cells, myeloid derived suppressor cells (MDSCs) are one kind of important immune suppression cells. They help tumor cells escape by inhibiting immune cells such as T cells or natural killer cells (NK cells). Research has found that the generation, differentiation, quantity, and apoptosis of MDSCs are closely related to the occurrence and development of digestive system tumors, and targeting MDSCs can be a potential point for targeted therapy. Therefore, this paper reviews the role of MDSCs in digestive system tumors and their targeted therapy research.
文章引用：黄丽葶, 刘姗姗. MDSCs在消化系统肿瘤中的作用及其靶向治疗的研究进展[J]. 临床医学进展, 2024, 14(9): 925-933. https://doi.org/10.12677/acm.2024.1492548

参考文献

[1] Sung, H., Ferlay, J., Siegel, R.L., Laversanne, M., Soerjomataram, I., Jemal, A., et al. (2021) Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: A Cancer Journal for Clinicians, 71, 209-249. [Google Scholar] [CrossRef] [PubMed]
[2] Tong, Y., Gao, H., Qi, Q., Liu, X., Li, J., Gao, J., et al. (2021) High Fat Diet, Gut Microbiome and Gastrointestinal Cancer. Theranostics, 11, 5889-5910. [Google Scholar] [CrossRef] [PubMed]
[3] Liu, Y., Baba, Y., Ishimoto, T., Gu, X., Zhang, J., Nomoto, D., et al. (2022) Gut Microbiome in Gastrointestinal Cancer: A Friend or Foe? International Journal of Biological Sciences, 18, 4101-4117. [Google Scholar] [CrossRef] [PubMed]
[4] Mima, K., Kosumi, K., Baba, Y., Hamada, T., Baba, H. and Ogino, S. (2020) The Microbiome, Genetics, and Gastrointestinal Neoplasms: The Evolving Field of Molecular Pathological Epidemiology to Analyze the Tumor-Immune-Microbiome Interaction. Human Genetics, 140, 725-746. [Google Scholar] [CrossRef] [PubMed]
[5] Hyde, A.J., Nassabein, R., AlShareef, A., Armstrong, D., Babak, S., Berry, S., et al. (2019) Eastern Canadian Gastrointestinal Cancer Consensus Conference 2018. Current Oncology, 26, 665-681. [Google Scholar] [CrossRef] [PubMed]
[6] Tumino, N., Besi, F., Martini, S., Di Pace, A.L., Munari, E., Quatrini, L., et al. (2022) Polymorphonuclear Myeloid-Derived Suppressor Cells Are Abundant in Peripheral Blood of Cancer Patients and Suppress Natural Killer Cell Anti-Tumor Activity. Frontiers in Immunology, 12, Article 803014. [Google Scholar] [CrossRef] [PubMed]
[7] Wang, Y., Jia, A., Bi, Y., Wang, Y. and Liu, G. (2020) Metabolic Regulation of Myeloid-Derived Suppressor Cell Function in Cancer. Cells, 9, Article 1011. [Google Scholar] [CrossRef] [PubMed]
[8] Wen, J., Xuan, B., Gao, Y., Liu, Y., Wang, L., He, L., et al. (2023) Lnc-17rik Promotes the Immunosuppressive Function of Myeloid-Derived Suppressive Cells in Esophageal Cancer. Cellular Immunology, 385, Article 104676. [Google Scholar] [CrossRef] [PubMed]
[9] Moaaz, M., Lotfy, H., Elsherbini, B., Motawea, M. and Fadali, G. (2020) TGF-β Enhances the Anti-Inflammatory Effect of Tumor-Infiltrating CD33+11b+HLA-DR Myeloid-Derived Suppressor Cells in Gastric Cancer: A Possible Relation to MicroRNA-494. Asian Pacific Journal of Cancer Prevention, 21, 3393-3403. [Google Scholar] [CrossRef] [PubMed]
[10] Ma, C., Zhang, Q. and Greten, T.F. (2021) MDSCs in Liver Cancer: A Critical Tumor-Promoting Player and a Potential Therapeutic Target. Cellular Immunology, 361, Article 104295. [Google Scholar] [CrossRef] [PubMed]
[11] Dong, P., Yan, Y., Fan, Y., Wang, H., Wu, D., Yang, L., et al. (2022) The Role of Myeloid-Derived Suppressor Cells in the Treatment of Pancreatic Cancer. Technology in Cancer Research & Treatment, 21. [Google Scholar] [CrossRef] [PubMed]
[12] Al-Mterin, M.A. and Elkord, E. (2022) Myeloid-Derived Suppressor Cells in Colorectal Cancer: Prognostic Biomarkers and Therapeutic Targets. Exploration of Targeted Anti-Tumor Therapy, 3, 497-510. [Google Scholar] [CrossRef] [PubMed]
[13] Mojsilovic, S., Mojsilovic, S.S., Bjelica, S. and Santibanez, J.F. (2021) Transforming Growth Factor‐Beta1 and Myeloid‐Derived Suppressor Cells: A Cancerous Partnership. Developmental Dynamics, 251, 85-104. [Google Scholar] [CrossRef] [PubMed]
[14] Stephen, J.K., Chen, K.M., Havard, S., Harris, G. and Worsham, M.J. (2012) Promoter Methylation in Head and Neck Tumorigenesis. In: Dumitrescu, R. and Verma, M., Eds., Cancer Epigenetics, Humana Press, 187-206. [Google Scholar] [CrossRef] [PubMed]
[15] Li, L., Li, M. and Jia, Q. (2023) Myeloid-Derived Suppressor Cells: Key Immunosuppressive Regulators and Therapeutic Targets in Cancer. Pathology-Research and Practice, 248, Article 154711. [Google Scholar] [CrossRef] [PubMed]
[16] Bayik, D., Lee, J. and Lathia, J.D. (2022) The Role of Myeloid-Derived Suppressor Cells in Tumor Growth and Metastasis. In: Klink, M. and Szulc-Kielbik, I., Eds., Interaction of Immune and Cancer Cells, Springer International Publishing, 189-217. [Google Scholar] [CrossRef] [PubMed]
[17] Hofer, F., Di Sario, G., Musiu, C., Sartoris, S., De Sanctis, F. and Ugel, S. (2021) A Complex Metabolic Network Confers Immunosuppressive Functions to Myeloid-Derived Suppressor Cells (MDSCs) within the Tumour Microenvironment. Cells, 10, Article 2700. [Google Scholar] [CrossRef] [PubMed]
[18] Umansky, V., Blattner, C., Fleming, V., Hu, X., Gebhardt, C., Altevogt, P., et al. (2016) Myeloid-Derived Suppressor Cells and Tumor Escape from Immune Surveillance. Seminars in Immunopathology, 39, 295-305. [Google Scholar] [CrossRef] [PubMed]
[19] Reuven, O., Mikula, I., Ashkenazi‐Preiser, H., Twaik, N., Ben‐Meir, K., Meirow, Y., et al. (2022) Functional Assays Evaluating Immunosuppression Mediated by Myeloid‐Derived Suppressor Cells. Current Protocols, 2, e557. [Google Scholar] [CrossRef] [PubMed]
[20] Beury, D.W., Carter, K.A., Nelson, C., Sinha, P., Hanson, E., Nyandjo, M., et al. (2016) Myeloid-Derived Suppressor Cell Survival and Function Are Regulated by the Transcription Factor Nrf2. The Journal of Immunology, 196, 3470-3478. [Google Scholar] [CrossRef] [PubMed]
[21] Ju, J., Nam, G., Lee, Y., Jung, M., Chang, H., Kim, W., et al. (2021) IDO1 Scavenges Reactive Oxygen Species in Myeloid-Derived Suppressor Cells to Prevent Graft-versus-Host Disease. Proceedings of the National Academy of Sciences, 118, e2011170118. [Google Scholar] [CrossRef] [PubMed]
[22] Tang, Y., Zhou, C., Li, Q., Cheng, X., Huang, T., Li, F., et al. (2022) Targeting Depletion of Myeloid-Derived Suppressor Cells Potentiates PD-L1 Blockade Efficacy in Gastric and Colon Cancers. OncoImmunology, 11, Article 2131084. [Google Scholar] [CrossRef] [PubMed]
[23] Ma, T., Renz, B.W., Ilmer, M., Koch, D., Yang, Y., Werner, J., et al. (2022) Myeloid-Derived Suppressor Cells in Solid Tumors. Cells, 11, Article 310. [Google Scholar] [CrossRef] [PubMed]
[24] Li, Y., He, H., Jihu, R., Zhou, J., Zeng, R. and Yan, H. (2021) Novel Characterization of Myeloid-Derived Suppressor Cells in Tumor Microenvironment. Frontiers in Cell and Developmental Biology, 9, Article 698532. [Google Scholar] [CrossRef] [PubMed]
[25] 叶萍萍. 免疫抑制性细胞MDSC、Treg、Ts在肿瘤患者外周血中的水平及其临床意义[D]: [硕士学位论文]. 郑州: 郑州大学, 2016.
[26] Jiao, Z. (2012) Correlation between Circulating Myeloid-Derived Suppressor Cells and Th17 Cells in Esophageal Cancer. World Journal of Gastroenterology, 18, 5454-5461. [Google Scholar] [CrossRef] [PubMed]
[27] Gabitass, R.F., Annels, N.E., Stocken, D.D., Pandha, H.A. and Middleton, G.W. (2011) Elevated Myeloid-Derived Suppressor Cells in Pancreatic, Esophageal and Gastric Cancer Are an Independent Prognostic Factor and Are Associated with Significant Elevation of the Th2 Cytokine Interleukin-13. Cancer Immunology, Immunotherapy, 60, 1419-1430. [Google Scholar] [CrossRef] [PubMed]
[28] Stoffel, E.M., Brand, R.E. and Goggins, M. (2023) Pancreatic Cancer: Changing Epidemiology and New Approaches to Risk Assessment, Early Detection, and Prevention. Gastroenterology, 164, 752-765. [Google Scholar] [CrossRef] [PubMed]
[29] Takeuchi, S., Baghdadi, M., Tsuchikawa, T., Wada, H., Nakamura, T., Abe, H., et al. (2015) Chemotherapy-Derived Inflammatory Responses Accelerate the Formation of Immunosuppressive Myeloid Cells in the Tissue Microenvironment of Human Pancreatic Cancer. Cancer Research, 75, 2629-2640. [Google Scholar] [CrossRef] [PubMed]
[30] Pergamo, M. and Miller, G. (2016) Myeloid-Derived Suppressor Cells and Their Role in Pancreatic Cancer. Cancer Gene Therapy, 24, 100-105. [Google Scholar] [CrossRef] [PubMed]
[31] Sharma, V., Aggarwal, A., Jacob, J. and Sahni, D. (2021) Myeloid‐Derived Suppressor Cells: Bridging the Gap between Inflammation and Pancreatic Adenocarcinoma. Scandinavian Journal of Immunology, 93, e13021. [Google Scholar] [CrossRef] [PubMed]
[32] Zhao, M., Tominaga, Y., Ohuchida, K., Mizumoto, K., Cui, L., Kozono, S., et al. (2011) Significance of Combination Therapy of Zoledronic Acid and Gemcitabine on Pancreatic Cancer. Cancer Science, 103, 58-66. [Google Scholar] [CrossRef] [PubMed]
[33] Ajani, J.A., D’Amico, T.A., Bentrem, D.J., Chao, J., Cooke, D., Corvera, C., et al. (2022) Gastric Cancer, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology. Journal of the National Comprehensive Cancer Network, 20, 167-192. [Google Scholar] [CrossRef] [PubMed]
[34] Jiménez-Cortegana, C., Galassi, C., Klapp, V., Gabrilovich, D.I. and Galluzzi, L. (2022) Myeloid-Derived Suppressor Cells and Radiotherapy. Cancer Immunology Research, 10, 545-557. [Google Scholar] [CrossRef] [PubMed]
[35] Wang, L., Chang, E.W.Y., Wong, S.C., Ong, S., Chong, D.Q.Y. and Ling, K.L. (2013) Increased Myeloid-Derived Suppressor Cells in Gastric Cancer Correlate with Cancer Stage and Plasma S100A8/A9 Proinflammatory Proteins. The Journal of Immunology, 190, 794-804. [Google Scholar] [CrossRef] [PubMed]
[36] Kao, K.D., Grasberger, H. and El-Zaatari, M. (2023) The Cxcr2+ Subset of the S100a8+ Gastric Granylocytic Myeloid-Derived Suppressor Cell Population (G-MDSC) Regulates Gastric Pathology. Frontiers in Immunology, 14, Article 1147695. [Google Scholar] [CrossRef] [PubMed]
[37] 王裕新, 潘凯枫, 李文庆. 2022全球癌症统计报告解读[J]. 肿瘤综合治疗电子杂志, 2024, 10(3): 1-16.
[38] Lu, C., Rong, D., Zhang, B., Zheng, W., Wang, X., Chen, Z., et al. (2019) Current Perspectives on the Immunosuppressive Tumor Microenvironment in Hepatocellular Carcinoma: Challenges and Opportunities. Molecular Cancer, 18, Article No. 130. [Google Scholar] [CrossRef] [PubMed]
[39] Yu, S.J., Ma, C., Heinrich, B., Brown, Z.J., Sandhu, M., Zhang, Q., et al. (2019) Targeting the Crosstalk between Cytokine-Induced Killer Cells and Myeloid-Derived Suppressor Cells in Hepatocellular Carcinoma. Journal of Hepatology, 70, 449-457. [Google Scholar] [CrossRef] [PubMed]
[40] Baidoun, F. (2021) Colorectal Cancer Epidemiology: Recent Trends and Impact on Outcomes. Current Drug Targets, 22, 998-1009. [Google Scholar] [CrossRef] 
[41] Lu, L., Chang, C. and Hsu, C. (2019) Targeting Myeloid-Derived Suppressor Cells in the Treatment of Hepatocellular Carcinoma: Current State and Future Perspectives. Journal of Hepatocellular Carcinoma, 6, 71-84. [Google Scholar] [CrossRef] [PubMed]
[42] Sun, H., Chen, J., Wu, W., Yang, Y., Xu, Y., Yu, X., et al. (2021) Retinoic Acid Synthesis Deficiency Fosters the Generation of Polymorphonuclear Myeloid-Derived Suppressor Cells in Colorectal Cancer. Cancer Immunology Research, 9, 20-33. [Google Scholar] [CrossRef] [PubMed]
[43] Li, K., Shi, H., Zhang, B., Ou, X., Ma, Q., Chen, Y., et al. (2021) Myeloid-Derived Suppressor Cells as Immunosuppressive Regulators and Therapeutic Targets in Cancer. Signal Transduction and Targeted Therapy, 6, Article No. 362. [Google Scholar] [CrossRef] [PubMed]
[44] Aarts, C.E.M. and Kuijpers, T.W. (2018) Neutrophils as Myeloid‐Derived Suppressor Cells. European Journal of Clinical Investigation, 48, e12989. [Google Scholar] [CrossRef] [PubMed]
[45] Fujita, M., Kohanbash, G., Fellows-Mayle, W., Hamilton, R.L., Komohara, Y., Decker, S.A., et al. (2011) COX-2 Blockade Suppresses Gliomagenesis by Inhibiting Myeloid-Derived Suppressor Cells. Cancer Research, 71, 2664-2674. [Google Scholar] [CrossRef] [PubMed]
[46] Noonan, K.A., Ghosh, N., Rudraraju, L., Bui, M. and Borrello, I. (2014) Targeting Immune Suppression with PDE5 Inhibition in End-Stage Multiple Myeloma. Cancer Immunology Research, 2, 725-731. [Google Scholar] [CrossRef] [PubMed]
[47] Draghiciu, O., Lubbers, J., Nijman, H.W. and Daemen, T. (2015) Myeloid Derived Suppressor Cells—An Overview of Combat Strategies to Increase Immunotherapy Efficacy. OncoImmunology, 4, e954829. [Google Scholar] [CrossRef] [PubMed]
[48] Safari, E., Ghorghanlu, S., Ahmadi‐khiavi, H., Mehranfar, S., Rezaei, R. and Motallebnezhad, M. (2018) Myeloid‐Derived Suppressor Cells and Tumor: Current Knowledge and Future Perspectives. Journal of Cellular Physiology, 234, 9966-9981. [Google Scholar] [CrossRef] [PubMed]
[49] Schwarz, J., Rühle, J., Stephan, K., Dietz, S., Geißert, J., Schoppmeier, U., et al. (2023) HIF‐1α Targeted Deletion in Myeloid Cells Decreases MDSC Accumulation and Alters Microbiome in Neonatal Mice. European Journal of Immunology, 53, Article 2250144. [Google Scholar] [CrossRef] [PubMed]
[50] Hossain, F., Al-Khami, A.A., Wyczechowska, D., Hernandez, C., Zheng, L., Reiss, K., et al. (2015) Inhibition of Fatty Acid Oxidation Modulates Immunosuppressive Functions of Myeloid-Derived Suppressor Cells and Enhances Cancer Therapies. Cancer Immunology Research, 3, 1236-1247. [Google Scholar] [CrossRef] [PubMed]
[51] Guo, C., Hu, F., Yi, H., Feng, Z., Li, C., Shi, L., et al. (2014) Myeloid-Derived Suppressor Cells Have a Proinflammatory Role in the Pathogenesis of Autoimmune Arthritis. Annals of the Rheumatic Diseases, 75, 278-285. [Google Scholar] [CrossRef] [PubMed]
[52] Dominguez, G.A., Condamine, T., Mony, S., Hashimoto, A., Wang, F., Liu, Q., et al. (2017) Selective Targeting of Myeloid-Derived Suppressor Cells in Cancer Patients Using DS-8273a, an Agonistic TRAIL-R2 Antibody. Clinical Cancer Research, 23, 2942-2950. [Google Scholar] [CrossRef] [PubMed]
[53] Qin, H., Lerman, B., Sakamaki, I., Wei, G., Cha, S.C., Rao, S.S., et al. (2014) Generation of a New Therapeutic Peptide That Depletes Myeloid-Derived Suppressor Cells in Tumor-Bearing Mice. Nature Medicine, 20, 676-681. [Google Scholar] [CrossRef] [PubMed]
[54] Feng, P., Yu, C., Chen, K., Luo, C., Wu, S.M., Liu, C., et al. (2018) S100A9+ MDSC and TAM-Mediated EGFR-TKI Resistance in Lung Adenocarcinoma: The Role of RELB. Oncotarget, 9, 7631-7643. [Google Scholar] [CrossRef] [PubMed]
[55] Vincent, J., Mignot, G., Chalmin, F., Ladoire, S., Bruchard, M., Chevriaux, A., et al. (2010) 5-Fluorouracil Selectively Kills Tumor-Associated Myeloid-Derived Suppressor Cells Resulting in Enhanced T Cell-Dependent Antitumor Immunity. Cancer Research, 70, 3052-3061. [Google Scholar] [CrossRef] [PubMed]
[56] Wu, Y., Yi, M., Niu, M., Mei, Q. and Wu, K. (2022) Myeloid-Derived Suppressor Cells: An Emerging Target for Anticancer Immunotherapy. Molecular Cancer, 21, Article No. 184. [Google Scholar] [CrossRef] [PubMed]

为你推荐