РОЛЬ ИММУННЫХ КЛЕТОК ПРИ РАКЕ ПЕЧЕНИ, СВЯЗАННОЙ С ОЖИРЕНИЕМ

Введение. Ожирение является установленным независимым фактором риска развития гепатоцеллюлярной карциномы – третьей по значимости причины смертности от онкологических заболеваний в мире. В Казахстане, где ожирением страдает более 20% взрослого населения, а заболеваемость раком печени неуклонно растёт, данная связь приобретает особую значимость для общественного здравоохранения. Несмотря на хорошо задокументированную эпидемиологическую взаимосвязь, механизмы, посредством которых ожирение нарушает противоопухолевый иммунитет и перестраивает микроокружение печени, остаются недостаточно изученными. В настоящем обзоре анализируется, каким образом популяции врождённого и адаптивного иммунитета подвергаются функциональному ремоделированию на протяжении континуума от неалкогольной жировой болезни печени до гепатоцеллюлярной карциномы в условиях хронического метаболического стресса.

Цель: Анализ современных научных данных о роли иммунных и воспалительных механизмов в развитии рака печени в контексте ожирения, а также систематизация сведений о том, каким образом метаболические нарушения влияют на противоопухолевый иммунный ответ и микроокружение печени.

Материалы и методы: Систематический поиск литературы проводился в международных базах данных PubMed, Google Scholar, Scopus и Web of Science и охватывал международные и отечественные публикации за период с 2000 по 2026 год.

Результаты и обсуждение: Гепатоцеллюлярной карцинома, ассоциированная с ожирением, развивается через прогрессирующий иммунометаболический каскад, при котором висцеральная жировая ткань формирует иммуносупрессивную микросреду – за счёт экспансии супрессорных клеток миелоидного происхождения (Myeloid-Derived Suppressor Cells, MDSC), дисфункции NK-клеток и истощения CD8+ T-лимфоцитов – ещё до начала злокачественной трансформации. Регуляторные T-клетки (Tregs) истощаются в жировой ткани при ожирении, однако накапливаются при гепатоцеллюлярной карциноме; активация NK-клеток при неалкогольном стеатогепатите приводит к повреждению гепатоцитов, а не к противоопухолевой защите. Определяющим фактором патологического исхода является функциональное состояние поляризации клеток, а не их количественная представленность

Выводы: Ожирение способствует развитию гепатоцеллюлярной карциномы через хроническое воспаление жировой ткани, инсулинорезистентность и метаболическое перепрограммирование опухолевого микроокружения, что приводит к истощению цитотоксических CD8⁺ T-клеток и NK-клеток при одновременном расширении иммуносупрессивных Treg и MDSC. Прогрессирование рака печени определяется не только вирусными или токсическими факторами, но и вызванным ожирением иммунным дисбалансом, при котором системный метаболический стресс становится ключевым фактором, способствующим ускользанию опухоли от иммунного надзора.

1. World Obesity Federation. (2023). World obesity atlas 2023. https://www.worldobesity.org/resources/resource-library/world-obesity-atlas-2023

2. Xie, J., Lin, X., Fan, X., Wang, X., Pan, D., Li, J., Hao, Y., Jie, Y., Zhang, L., & Gu, J. (2024). Global burden and trends of primary liver cancer attributable to comorbid type 2 diabetes mellitus among people living with hepatitis B: An observational trend study from 1990 to 2019. Journal of Epidemiology and Global Health, 14(2), 398–410. https://doi.org/10.1007/s44197-024-00237-1

3. Ablayeva, A., Syssoyev, D., Akhmedullin, R., Beyembetova, A., Abdukhakimova, D., Aimyshev, T., Arupzhanov, I., Zhakhina, G., Biniyazova, A., Seyil, T., Igissin, N., Semenova, Y., & Gaipov, A. (2025). Epidemiology of liver cancer in Kazakhstan: Data from the Unified National Electronic Health System, 2014–2023. PLoS ONE, 20(8), e0330423. https://doi.org/10.1371/journal.pone.0330423

4. World Health Organization. (2025). Obesity and overweight. https://www.who.int/en/news-room/fact-sheets/detail/obesity-and-overweight

5. Shalgumbayeva, G., Sailauova, N., Sharapiyeva, A., Romanova, E., Akhmetova, K., Balashkevich, N., Pronin, E., Chalaya, E., Tyupa, P., & Aganov, S. (2023). Characteristics of physical activity in the adult population with different risk of overweight and obesity (illustrated by the case of Kazakhstan). Journal of Physical Education and Sport, 23(11), 3003–3008. https://doi.org/10.7752/jpes.2023.11341

6. Corica, D., Aversa, T., Valenzise, M. F., Messina, M. F., Alibrandi, A., De Luca, F., & Wasniewska, M. (2018). Does family history of obesity, cardiovascular, and metabolic diseases influence onset and severity of childhood obesity? Frontiers in Endocrinology, 9, 187. https://doi.org/10.3389/fendo.2018.00187

7. Farzand, A., Rohin, M. A. K., Awan, S. J., Sharif, Z., Yaseen, A., & Ahmad, A. M. R. (2025). A review of syndromic forms of obesity: Genetic etiology, clinical features, and molecular diagnosis. Current Issues in Molecular Biology, 47(9), 718. https://doi.org/10.3390/cimb47090718

8. Dubern, B., Mosbah, H., Pigeyre, M., Clément, K., & Poitou, C. (2022). Rare genetic causes of obesity: Diagnosis and management in clinical care. Annales d'Endocrinologie, 83(1), 63–72. https://doi.org/10.1016/j.ando.2021.12.003

9. Rajesh, Y., & Sarkar, D. (2021). Association of adipose tissue and adipokines with development of obesity-induced liver cancer. International Journal of Molecular Sciences, 22(4), 2163. https://doi.org/10.3390/ijms22042163

10. Løvsletten, O., Jacobsen, B. K., Grimsgaard, S., Njølstad, I., Wilsgaard, T., Løchen, M. L., Eggen, A. E., & Hopstock, L. A. (2020). Prevalence of general and abdominal obesity in 2015–2016 and 8-year longitudinal weight and waist circumference changes in adults and elderly: The Tromsø Study. BMJ Open, 10(11), e038465. https://doi.org/10.1136/bmjopen-2020-038465

11. Liu, B. N., Liu, X. T., Liang, Z. H., & Wang, J. H. (2021). Gut microbiota in obesity. World Journal of Gastroenterology, 27(25), 3837–3850. https://doi.org/10.3748/wjg.v27.i25.3837

12. Pati, S., Irfan, W., Jameel, A., Ahmed, S., & Shahid, R. K. (2023). Obesity and cancer: A current overview of epidemiology, pathogenesis, outcomes, and management. Cancers, 15(2), 485. https://doi.org/10.3390/cancers15020485

13. Annett, S., Moore, G., & Robson, T. (2020). Obesity and cancer metastasis: Molecular and translational perspectives. Cancers, 12(12), 3798. https://doi.org/10.3390/cancers12123798

14. Guo, C., Liu, Z., Lin, C., Fan, H., Zhang, X., Wang, H., Han, X., Li, Y., Mu, L., Yu, S., & Zhang, T. (2023). Global epidemiology of early-onset liver cancer attributable to specific aetiologies and risk factors from 2010 to 2019. Journal of Global Health, 13, 04167. https://doi.org/10.7189/jogh.13.04167

15. O'Rourke, J. M., Sagar, V. M., Shah, T., & Shetty, S. (2018). Carcinogenesis on the background of liver fibrosis: Implications for the management of hepatocellular cancer. World Journal of Gastroenterology, 24(39), 4436–4447. https://doi.org/10.3748/wjg.v24.i39.4436

16. Siegel, R. L., Kratzer, T. B., Giaquinto, A. N., Sung, H., & Jemal, A. (2025). Cancer statistics, 2025. CA: A Cancer Journal for Clinicians, 75(1), 10–45. https://doi.org/10.3322/caac.21871

17. Burkitbayev, Z., Akhmedullin, R., Zharlyganova, D., Manatova, A., Kuanysh, Z., Shalekenov, S., Kim, A., & Gaipov, A. (2026). Cancer trends in Central Asia from 1990 to 2021: Analysis of the Global Burden of Disease Study. Electronic Journal of General Medicine, 23(2), em718. https://doi.org/10.29333/ejgm/17973

18. Malayev, N., Saparbayev, S., Kubekova, S., & Zhampeissov, N. (2023). Actual issues of secondary prevention of liver cancer in Kazakhstan. Journal of Clinical Medicine of Kazakhstan, 20(6), 66–72. https://doi.org/10.23950/jcmk/13926

19. Li, X., Ramadori, P., Pfister, D., Seehawer, M., Zender, L., & Heikenwalder, M. (2021). The immunological and metabolic landscape in primary and metastatic liver cancer. Nature Reviews Cancer, 21(9), 541–557. https://doi.org/10.1038/s41568-021-00383-9

20. Chalasani, N., Younossi, Z., Lavine, J. E., Charlton, M., Cusi, K., Rinella, M., Harrison, S. A., Brunt, E. M., & Sanyal, A. J. (2018). The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases. Hepatology, 67(1), 328–357. https://doi.org/10.1002/hep.29367

21. Estes, C., Razavi, H., Loomba, R., Younossi, Z., & Sanyal, A. J. (2018). Modeling the epidemic of nonalcoholic fatty liver disease demonstrates an exponential increase in burden of disease. Hepatology, 67(1), 123–133. https://doi.org/10.1002/hep.29466

22. Divella, R., Mazzocca, A., Daniele, A., Sabbà, C., & Paradiso, A. (2019). Obesity, nonalcoholic fatty liver disease and adipocytokines network in promotion of cancer. International Journal of Biological Sciences, 15(3), 610–616. https://doi.org/10.7150/ijbs.29599

23. Hopkins, B. D., Goncalves, M. D., & Cantley, L. C. (2016). Obesity and cancer mechanisms: Cancer metabolism. Journal of Clinical Oncology, 34(35), 4277–4283. https://doi.org/10.1200/JCO.2016.67.9712

24. Ioannou, G. N. (2016). The role of cholesterol in the pathogenesis of NASH. Trends in Endocrinology & Metabolism, 27(2), 84–95. https://doi.org/10.1016/j.tem.2015.11.008

25. Lega, I. C., Wilton, A. S., Austin, P. C., Fischer, H. D., Johnson, J. A., & Lipscombe, L. L. (2016). The temporal relationship between diabetes and cancer: A population-based study. Cancer, 122(17), 2731–2738. https://doi.org/10.1002/cncr.30095

26. Nishikawa, H., Shiraki, M., Hiramatsu, A., Moriya, K., Hino, K., & Nishiguchi, S. (2016). Japan Society of Hepatology guidelines for sarcopenia in liver disease (1st edition): Recommendation from the working group for creation of sarcopenia assessment criteria. Hepatology Research, 46(10), 951–963. https://doi.org/10.1111/hepr.12774

27. Ding, W., Xu, X., Qian, Y., Xue, W., Wang, Y., Du, J., Jin, L., & Tan, Y. (2018). Prognostic value of tumor-infiltrating lymphocytes in hepatocellular carcinoma: A meta-analysis. Medicine, 97(50), e13301. https://doi.org/10.1097/MD.0000000000013301

28. Ilyas, S. I., Wang, J., & El-Khoueiry, A. B. (2021). Liver cancer immunity. Hepatology, 73(Suppl. 1), 86–103. https://doi.org/10.1002/hep.31416

29. Ringelhan, M., Pfister, D., O'Connor, T., Pikarsky, E., & Heikenwalder, M. (2018). The immunology of hepatocellular carcinoma. Nature Immunology, 19(3), 222–232. https://doi.org/10.1038/s41590-018-0044-z

30. Wang, Q., & Wu, H. (2018). T cells in adipose tissue: Critical players in immunometabolism. Frontiers in Immunology, 9, 2509. https://doi.org/10.3389/fimmu.2018.02509

31. Wang, Q., Wang, Y., & Xu, D. (2021). The roles of T cells in obese adipose tissue inflammation. Adipocyte, 10(1), 435–445. https://doi.org/10.1080/21623945.2021.1965314

32. Breuer, D. A., Pacheco, M. C., Washington, M. K., Montgomery, S. A., Hasty, A. H., & Kennedy, A. J. (2020). CD8+ T cells regulate liver injury in obesity-related nonalcoholic fatty liver disease. American Journal of Physiology-Gastrointestinal and Liver Physiology, 318(2), G211–G224. https://doi.org/10.1152/ajpgi.00040.2019

33. Lurje, I., Hammerich, L., & Tacke, F. (2020). Dendritic cell and T cell crosstalk in liver fibrogenesis and hepatocarcinogenesis: Implications for prevention and therapy of liver cancer. International Journal of Molecular Sciences, 21(19), 7378. https://doi.org/10.3390/ijms21197378

34. Montauti, E., Oh, D. Y., & Fong, L. (2024). CD4⁺ T cells in antitumor immunity. Trends in Cancer, 10(10), 969–985. https://doi.org/10.1016/j.trecan.2024.07.009

35. Yamada, K., Saito, M., Ando, M., Abe, T., Mukoyama, T., Agawa, K., Watanabe, A., Takamura, S., Fujita, M., Urakawa, N., Hasegawa, H., Kanaji, S., Matsuda, T., Oshikiri, T., Kakeji, Y., & Yamashita, K. (2022). Reduced number and immune dysfunction of CD4+ T cells in obesity accelerate colorectal cancer progression. Cells, 12(1), 86. https://doi.org/10.3390/cells12010086

36. Sutti, S., & Albano, E. (2020). Adaptive immunity: An emerging player in the progression of NAFLD. Nature Reviews Gastroenterology & Hepatology, 17(2), 81–92. https://doi.org/10.1038/s41575-019-0210-2

37. Miao, Y., Li, Z., Feng, J., Lei, X., Shan, J., Qian, C., & Li, J. (2024). The role of CD4+ T cells in nonalcoholic steatohepatitis and hepatocellular carcinoma. International Journal of Molecular Sciences, 25(13), 6895. https://doi.org/10.3390/ijms25136895

38. Chaoul, N., Mancarella, S., Lupo, L., Giannelli, G., & Dituri, F. (2020). Impaired antitumor T cell response in hepatocellular carcinoma. Cancers, 12(3), 627. https://doi.org/10.3390/cancers12030627

39. Mendoza-Pérez, A., Vitales-Noyola, M., González-Baranda, L., Álvarez-Quiroga, C., Hernández-Castro, B., Monsiváis-Urenda, A., Baranda, L., Niño-Moreno, P., Hurtado, G., Sánchez-Gutiérrez, R., & González-Amaro, R. (2022). Increased levels of pathogenic Th17 cells and diminished function of CD69+ Treg lymphocytes in patients with overweight. Clinical & Experimental Immunology, 209(1), 115–125. https://doi.org/10.1093/cei/uxac051

40. Dituri, F., Mancarella, S., Serino, G., Chaoul, N., Lupo, L. G., Villa, E., Fabregat, I., & Giannelli, G. (2021). Direct and indirect effect of TGFβ on Treg transendothelial recruitment in HCC tissue microenvironment. International Journal of Molecular Sciences, 22(21), 11765. https://doi.org/10.3390/ijms222111765

41. Cairoli, V., De Matteo, E., Rios, D., Lezama, C., Galoppo, M., Casciato, P., Mullen, E., Giadans, C., Bertot, G., Preciado, M. V., & Valva, P. (2021). Hepatic lymphocytes involved in the pathogenesis of pediatric and adult nonalcoholic fatty liver disease. Scientific Reports, 11(1), Article 5129. https://doi.org/10.1038/s41598-021-84674-z

42. Dywicki, J., Buitrago-Molina, L. E., Noyan, F., Davalos-Misslitz, A. C., Hupa-Breier, K. L., Lieber, M., Hapke, M., Schlue, J., Falk, C. S., Raha, S., Prinz, I., Koenecke, C., Manns, M. P., Wedemeyer, H., Hardtke-Wolenski, M., & Jaeckel, E. (2022). The detrimental role of regulatory T cells in nonalcoholic steatohepatitis. Hepatology Communications, 6(2), 320–333. https://doi.org/10.1002/hep4.1807

43. Raheem, A., Khan, I., Ahmad, I., Wajid, A., Alshahrani, M. Y., Alzahrani, F. M., Alzahrani, K. J., Qadeer, A., Liao, I. C., & Chen, C. C. (2025). The emerging role of tissue regulatory T cells in tissue repair and regeneration. Frontiers in Immunology, 16, Article 1640113. https://doi.org/10.3389/fimmu.2025.1640113

44. Zhang, C. Y., Liu, S., & Yang, M. (2022). Regulatory T cells and their associated factors in hepatocellular carcinoma development and therapy. World Journal of Gastroenterology, 28(27), 3346–3358. https://doi.org/10.3748/wjg.v28.i27.3346

45. Spielmann, J., Hanke, J., Knauf, D., Ben-Eliyahu, S., Jacobs, R., Stangl, G. I., Bähr, I., & Kielstein, H. (2017). Significantly enhanced lung metastasis and reduced organ NK cell functions in diet-induced obese rats. BMC Obesity, 4, Article 24. https://doi.org/10.1186/s40608-017-0161-5

46. Kaur, K., Chang, H. H., Topchyan, P., Cook, J. M., Barkhordarian, A., Eibl, G., & Jewett, A. (2018). Deficiencies in natural killer cell numbers, expansion, and function at the pre-neoplastic stage of pancreatic cancer by KRAS mutation in the pancreas of obese mice. Frontiers in Immunology, 9, Article 1229. https://doi.org/10.3389/fimmu.2018.01229

47. Viel, S., Besson, L., Charrier, E., Marçais, A., Disse, E., Bienvenu, J., Walzer, T., & Dumontet, C. (2017). Alteration of natural killer cell phenotype and function in obese individuals. Clinical Immunology, 177, 12–17. https://doi.org/10.1016/j.clim.2016.01.007

48. Diedrich, T., Kummer, S., Galante, A., Drolz, A., Schlicker, V., Lohse, A. W., Kluwe, J., Eberhard, J. M., & Schulze Zur Wiesch, J. (2020). Characterization of the immune cell landscape of patients with NAFLD. PLoS ONE, 15(3), Article e0230307. https://doi.org/10.1371/journal.pone.0230307

49. Wang, F., Zhang, X., Liu, W., Zhou, Y., Wei, W., Liu, D., Wong, C. C., Sung, J. J. Y., & Yu, J. (2022). Activated natural killer cell promotes nonalcoholic steatohepatitis through mediating JAK/STAT pathway. Cellular and Molecular Gastroenterology and Hepatology, 13(1), 257–274. https://doi.org/10.1016/j.jcmgh.2021.08.019

50. Polidoro, M. A., Mikulak, J., Cazzetta, V., Lleo, A., Mavilio, D., Torzilli, G., & Donadon, M. (2020). Tumor microenvironment in primary liver tumors: A challenging role of natural killer cells. World Journal of Gastroenterology, 26(33), 4900–4918. https://doi.org/10.3748/wjg.v26.i33.4900

51. Wu, M., Mei, F., Liu, W., & Jiang, J. (2020). Comprehensive characterization of tumor infiltrating natural killer cells and clinical significance in hepatocellular carcinoma based on gene expression profiles. Biomedicine & Pharmacotherapy, 121, Article 109637. https://doi.org/10.1016/j.biopha.2019.109637

52. Boutens, L., & Stienstra, R. (2016). Adipose tissue macrophages: Going off track during obesity. Diabetologia, 59, 879–894. https://doi.org/10.1007/s00125-016-3904-9

53. Daemen, S., & Schilling, J. D. (2020). The interplay between tissue niche and macrophage cellular metabolism in obesity. Frontiers in Immunology, 10, Article 3133. https://doi.org/10.3389/fimmu.2019.03133

54. Bohn, T., Rapp, S., Luther, N., Klein, M., Bruehl, T. J., Kojima, N., Aranda Lopez, P., Hahlbrock, J., Muth, S., Endo, S., Pektor, S., Brand, A., Renner, K., Popp, V., Gerlach, K., Vogel, D., Lueckel, C., Arnold-Schild, D., Pouyssegur, J., Kreutz, M., Huber, M., Koenig, J., Weigmann, B., Probst, H. C., von Stebut, E., Becker, C., Schild, H., Schmitt, E., & Bopp, T. (2018). Tumor immunoevasion via acidosis-dependent induction of regulatory tumor-associated macrophages. Nature Immunology, 19(12), 1319–1329. https://doi.org/10.1038/s41590-018-0226-8

55. Krenkel, O., & Tacke, F. (2017). Liver macrophages in tissue homeostasis and disease. Nature Reviews Immunology, 17(5), 306–321. https://doi.org/10.1038/nri.2017.11

56. Zang, M., Li, Y., He, H., Ding, H., Chen, K., Du, J., Chen, T., Wu, Z., Liu, H., Wang, D., Cai, J., & Qu, C. (2018). IL-23 production of liver inflammatory macrophages to damaged hepatocytes promotes hepatocellular carcinoma development after chronic hepatitis B virus infection. Biochimica et Biophysica Acta: Molecular Basis of Disease, 1864(12), 3759–3770. https://doi.org/10.1016/j.bbadis.2018.10.004

57. Arvanitakis, K., Koletsa, T., Mitroulis, I., & Germanidis, G. (2022). Tumor-associated macrophages in hepatocellular carcinoma pathogenesis, prognosis and therapy. Cancers, 14(1), Article 226. https://doi.org/10.3390/cancers14010226

58. Hildreth, A. D., Ma, F., Wong, Y. Y., Sun, R., Pellegrini, M., & O'Sullivan, T. E. (2021). Single-cell sequencing of human white adipose tissue identifies new cell states in health and obesity. Nature Immunology, 22(5), 639–653. https://doi.org/10.1038/s41590-021-00922-4

59. Lee, A. H., & Dixit, V. D. (2020). Dietary regulation of immunity. Immunity, 53(3), 510–523. https://doi.org/10.1016/j.immuni.2020.08.013

60. Engin, A. (2017). Human protein kinases and obesity. Advances in Experimental Medicine and Biology, 960, 111–134. https://doi.org/10.1007/978-3-319-48382-5_5

61. Martín-Sierra, C., Martins, R., Laranjeira, P., Abrantes, A. M., Oliveira, R. C., Tralhão, J. G., Botelho, M. F., Furtado, E., Domingues, R., & Paiva, A. (2019). Functional impairment of circulating FcεRI+ monocytes and myeloid dendritic cells in hepatocellular carcinoma and cholangiocarcinoma patients. Cytometry Part B: Clinical Cytometry, 96(6), 490–495. https://doi.org/10.1002/cyto.b.21777

62. Li, W., Chen, G., Peng, H., Zhang, Q., Nie, D., Guo, T., Zhu, Y., Zhang, Y., & Lin, M. (2024). Research progress on dendritic cells in hepatocellular carcinoma immune microenvironments. Biomolecules, 14(9), Article 1161. https://doi.org/10.3390/biom14091161

63. Zhou, Z. J., Xin, H. Y., Li, J., Hu, Z. Q., Luo, C. B., & Zhou, S. L. (2019). Intratumoral plasmacytoid dendritic cells as a poor prognostic factor for hepatocellular carcinoma following curative resection. Cancer Immunology, Immunotherapy, 68(8), 1223–1233. https://doi.org/10.1007/s00262-019-02355-3

64. Elwan, N., Salem, M. L., Kobtan, A., El-Kalla, F., Mansour, L., Yousef, M., Al-Sabbagh, A., Zidan, A. A., & Abd-Elsalam, S. (2018). High numbers of myeloid derived suppressor cells in peripheral blood and ascitic fluid of cirrhotic and HCC patients. Immunological Investigations, 47(2), 169–180. https://doi.org/10.1080/08820139.2017.1407787

65. Turbitt, W. J., Collins, S. D., Meng, H., & Rogers, C. J. (2019). Increased adiposity enhances the accumulation of MDSCs in the tumor microenvironment and adipose tissue of pancreatic tumor-bearing mice and in immune organs of tumor-free hosts. Nutrients, 11(12), Article 3012. https://doi.org/10.3390/nu11123012

66. Sun, Q., Dai, H., Wang, S., Chen, Y., & Shi, H. (2023). Progress in research on the role played by myeloid-derived suppressor cells in liver diseases. Scandinavian Journal of Immunology, 98(4), Article e13312. https://doi.org/10.1111/sji.13312

67. Deng, X., Li, X., Guo, X., Lu, Y., Xie, Y., Huang, X., Lin, J., Tan, W., & Wang, C. (2022). Myeloid-derived suppressor cells promote tumor growth and sorafenib resistance by inducing FGF1 upregulation and fibrosis. Neoplasia, 28, Article 100788. https://doi.org/10.1016/j.neo.2022.100788

68. Li, T., Zhang, X., Lv, Z., Gao, L., & Yan, H. (2020). Increased expression of myeloid-derived suppressor cells in patients with HBV-related hepatocellular carcinoma. BioMed Research International, 2020, Article 6527192. https://doi.org/10.1155/2020/6527192