Значение макрофагов, ассоциированных с опухолью, в развитии рака мочевого пузыря

Рак мочевого пузыря занимает 2-е место в структуре онкоурологических заболеваний во всем мире. выделяют мышечно-инвазивную и немышечно-инвазивную формы опухоли. в последнее время большое внимание уделяется изучению микроокружения опухоли (МО) при злокачественных новообразованиях мочевого пузыря. Согласно имеющимся на сегодняшний день данным, МО представляет собой специфическую среду, создающую оптимальные условия для канцерогенеза в неопластическом очаге. Основными частями МО являются внеклеточный матрикс и строма, которая включает сосуды, стромальные и иммунные клетки. помимо данных структур в состав МО входят цитокины, хемокины и другие соединения, способные обеспечивать активацию необходимых для опухолевых клеток сигнальных путей. Макрофаги, ассоциированные с опухолью (МАО), - активно изучаемые представители МО при солидных злокачественных новообразованиях различных локализаций. эти макрофаги подразделяют на 2 фенотипа: M1 (провоспалительные и противоопухолевые) и M2 (противовоспалительные и проопухолевые). Роль каждого фенотипа различна, при этом макрофаги M2 участвуют в регуляции важнейших процессов онкогенеза (инвазии, пролиферации, неоангиогенезе и т. д.). в аспекте изучения рака мочевого пузыря наибольшую значимость имеют макрофаги M2, которые являются самыми многочисленными представителями МАО в составе МО.

Цель исследования - изучение роли макрофагов, ассоциированных с опухолью, в развитии злокачественных опухолей мочевого пузыря, а также их прогностической ценности.

1. Antoni S., Ferlay J., Soerjomataram I. et al. Bladder cancer incidence and mortality: a global overview and recent trends. Eur Urol 2017;71(1):96-108. DOI: 10.1016/j.eururo.2016.06.010

2. Ohishi T., Koga F., Migita T. Bladder cancer stem-like cells: their origin and therapeutic perspectives. Int J Mol Sci 2015;17(1):43. DOI: 10.3390/ijms17010043

3. Apodaca G. The uroepithelium: not just a passive barrier. Traffic 2004;5(3):117-28. DOI: 10.1046/j.1600-0854.2003.00156.x

4. Khandelwal P., Abraham S.N., Apodaca G. Cell biology and physiology of the uroepithelium. Am J Physiol Renal Physiol 2009;297(6):F1477-501. DOI: 10.1152/ajprenal.00327.2009

5. Kurzrock E.A., Lieu D.K., Degraffenried L.A. et al. Label-retaining cells of the bladder: candidate urothelial stem cells. Am J Physiol Renal Physiol 2008;294(6):F1415-21. DOI: 10.1152/ajprenal.00533.2007

6. Chulpanova D.S., Kitaeva K.V., Green A.R. et al. Molecular aspects and future perspectives of cytokine-based anti-cancer immunotherapy. Front Cell Dev Biol 2020;8(402):1-24. DOI: 10.3389/fcell.2020.00402

7. Xue Y., Tong L., Liu F. et al. Tumor-infiltrating M2 macrophages driven by specific genomic alterations are associated with prognosis in bladder cancer. Oncol Rep 2019;42(2):581-94. DOI: 10.3892/or.2019.7196

8. Şenbabaoğlu Y., Gejman R.S., Winer A.G. et al. Tumor immune microenvironment characterization in clear cell renal cell carcinoma identifies prognostic and immunotherapeutically relevant messenger RNA signatures. Genome Biol 2016;17:231. DOI: 10.1186/s13059-016-1092-z

9. Wang M., Zhao J., Zhang L. et al. Role of tumor microenvironment in tumorigenesis. J Cancer. 2017;8(5):761-73. DOI: 10.7150/jca.17648

10. Ocana M.C., Martmez-Poveda B., Quesada A.R. et al. Metabolism within the tumor microenvironment and its implication on cancer progression: an ongoing therapeutic target. Med Res Rev 2019;39(1):70-113. DOI: 10.1002/med.21511

11. Hatogai K., Sweis R.F. The tumor microenvironment of bladder cancer. Adv Exp Med Biol 2020;1296:275-90. DOI: 10.1007/978-3-030-59038-3_17

12. Haniffa M., Bigley V., Collin M. Human mononuclear phagocyte system reunited. Semin Cell Dev Biol 2015;41:59-69. DOI: 10.1016/j.semcdb.2015.05.004

13. Locati M., Curtale G., Mantovani A. Diversity, mechanisms, and significance of macrophage plasticity. Annu Rev Pathol 2020;15:123-47. DOI: 10.1146/annurev-pathmechdis-012418-012718

14. Yang L., Zhang Y. Tumor-associated macrophages: from basic research to clinical application. J Hematol Oncol 2017;10(1):58. DOI: 10.1186/s13045-017-0430-2

15. Zhu S., Luo Z., Li X. et al. Tumor-associated macrophages: role in tumorigenesis and immunotherapy implications. J Cancer 2021;12(1):54-64. DOI: 10.7150/jca.49692

16. Morrison C. Immuno-oncologists eye up macrophage targets. Nat Rev Drug Discov 2016;15(6):373-4. DOI: 10.1038/nrd.2016.111

17. Wang N., Liang H., Zen K. Molecular mechanisms that influence the macrophage m1-m2 polarization balance. Front Immunol. 2014;5:614. DOI: 10.3389/fimmu.2014.00614

18. Qian B.Z., Pollard J.W. Macrophage diversity enhances tumor progression and metastasis. Cell 2010;141(1):39-51. DOI: 10.1016/j.cell.2010.03.014

19. Najafi M., Hashemi Goradel N., Farhood B. et al. Macrophage polarity in cancer: a review. J Cell Biochem 2019;120(3):2756-65. DOI: 10.1002/jcb.27646

20. Arnold C.E., Whyte C.S., Gordon P. et al. A critical role for suppressor of cytokine signalling 3 in promoting M1 macrophage activation and function in vitro and in vivo. Immunology 2014;141(1):96-110. DOI: 10.1111/imm.12173

21. Chanmee T., Ontong P., Konno K. et al. Tumor-associated macrophages as major players in the tumor microenvironment. Cancers (Basel) 2014;6(3):1670-90. DOI: 10.3390/cancers6031670

22. Brown J.M., Recht L., Strober S. The promise of targeting macrophages in cancer therapy. Clin Cancer Res 2017;23(13): 3241-50. DOI: 10.1158/1078-0432.CCR-16-3122

23. Zhou J., Tang Z., Gao S. et al. Tumor-associated macrophages: recent insights and therapies. Front Oncol 2020;10:188. DOI: 10.3389/fonc.2020.00188

24. Costa N.L., Valadares M.C., Souza P.P.C. et al. Tumor-associated macrophages and the profile of inflammatory cytokines in oral squamous cell carcinoma. Oral Oncol 2013;49:216-23. DOI: 10.1016/j.oraloncology.2012.09.012

25. Sica A., Mantovani A. Macrophage plasticity and polarization: in vivo veritas. J Clin Invest 2012;122(3):787-95. DOI: 10.1172/JCI59643

26. Hughes R., Qian B.Z., Rowan C. et al. Perivascular M2 macrophages stimulate tumor relapse after chemotherapy. Cancer Res 2015;75(17):3479-91. DOI: 10.1158/0008-5472.CAN-14-3587

27. Zhang W., Wang L., Zhou D. et al. Expression of tumor-associated macrophages and vascular endothelial growth factor correlates with poor prognosis of peripheral T-cell lymphoma, not otherwise specified. Leuk Lymphoma 2011;52(1):46-52. DOI: 10.3109/10428194.2010.529204

28. Fu H., Zhu Y., Wang Y. et al. Identification and validation of stromal immunotype predict survival and benefit from adjuvant chemotherapy in patients with muscle-invasive bladder cancer. Clin Cancer Res 2018;24(13):3069-78. DOI: 10.1158/1078-0432.CCR-17-2687

29. Wang B., Liu H., Dong X. et al. High CD204+ tumor-infiltrating macrophage density predicts a poor prognosis in patients with urothelial cell carcinoma of the bladder. Oncotarget 2015;6(24):20204-14. DOI: 10.18632/oncotarget.3887

30. Zhang H., Ye Y.L., Li M.X. et al. CXCL2/MIF-CXCR2 signaling promotes the recruitment of myeloid-derived suppressor cells and is correlated with prognosis in bladder cancer. Oncogene 2017;36(15):2095-104. DOI: 10.1038/onc.2016.367

31. Qiu S., Deng L., Liao X. et al. Tumor-associated macrophages promote bladder tumor growth through PI3K/AKT signal induced by collagen. Cancer Sci 2019;110(7):2110-8. DOI: 10.1111/cas.14078

32. Leblond M.M., Zdimerova H., Desponds E. et al. Tumor-associated macrophages in bladder cancer: biological role, impact on therapeutic response and perspectives for immunotherapy. Cancers (Basel) 2021;13(18):4712. DOI: 10.3390/cancers13184712

33. Cheah M.T., Chen J.Y., Sahoo D. et al. CD14-expressing cancer cells establish the inflammatory and proliferative tumor microenvironment in bladder cancer. Proc Natl Acad Sci USA. 2015;112(15):4725-30. DOI: 10.1073/pnas.1424795112

34. Martmez V.G., Rubio C., Martinez-Fernandez M. et al. BMP4 induces M2 macrophage polarization and favors tumor progression in bladder cancer. Clin Cancer Res 2017;23(23):7388-99. DOI: 10.1158/1078-0432.CCR-17-1004

35. Prima V., Kaliberova L.N., Kaliberov S. et al. COX2/mPGES1/ PGE2 pathway regulates PD-L1 expression in tumor-associated macrophages and myeloid-derived suppressor cells. Proc Natl Acad Sci USA 2017;114(5):1117-22. DOI: 10.1073/pnas.1612920114

36. Wu A.T.H., Srivastava P., Yadav V.K. et al. Ovatodiolide, isolated from Anisomeles indica, suppresses bladder carcinogenesis through suppression of mTOR/e-catenin/CDK6 and exosomal miR-21 derived from M2 tumor-associated macrophages. Toxicol Appl Pharmacol. 2020;401:115109. DOI: 10.1016/j.taap.2020.115109

37. Wang X., Ni S., Chen Q. et al. Bladder cancer cells induce immunosuppression of T cells by supporting PD-L1 expression in tumour macrophages partially through interleukin 10. Cell Biol Int 2017;41(2):177-86. DOI: 10.1002/cbin.10716

38. Zhao Y., Wang D., Xu T. et al. Bladder cancer cells re-educate TAMs through lactate shuttling in the microfluidic cancer microenvironment. Oncotarget 2015;6(36):39196-210. DOI: 10.18632/oncotarget.5538

39. Reusser N.M., Dalton H.J., Pradeep S. et al. Clodronate inhibits tumor angiogenesis in mouse models of ovarian cancer. Cancer Biol Ther 2014;15(8):1061-7. DOI: 10.4161/cbt.29184

40. Zhang Q., Mao Z., Sun J. NF-kB inhibitor, BAY11-7082, suppresses M2 tumor-associated macrophage induced EMT potential via miR-30a/NF-kB/Snail signaling in bladder cancer cells. Gene 2019;710:91-7. DOI: 10.1016/j.gene.2019.04.039

41. Wu H., Zhang X., Han D. et al. Tumour-associated macrophages mediate the invasion and metastasis of bladder cancer cells through CXCL8. Peer J 2020;8:e8721. DOI: 10.7717/peerj.8721

42. Dominguez-Gutierrez P.R., Kwenda E.P., Donelan W. et al. Hyal2 expression in tumor-associated myeloid cells mediates cancer-related inflammation in bladder cancer. Cancer Res 2021;81(3):648-57. DOI: 10.1158/0008-5472.CAN-20-1144

43. Chen C., He W., Huang J. et al. LNMAT1 promotes lymphatic metastasis of bladder cancer via CCL2 dependent macrophage recruitment. Nat Commun 2018;9(1):3826. DOI: 10.1038/s41467-018-06152-x

44. Huang C.P., Liu L.X., Shyr C.R. Tumor-associated macrophages facilitate bladder cancer progression by increasing cell growth, migration, invasion and cytokine expression. Anticancer Res 2020;40(5):2715-24. DOI: 10.21873/anticanres.14243

45. Lin F., Yin H.B., Li X.Y. et al. Bladder cancer cell-secreted exosomal miR-21 activates the PI3K/AKT pathway in macrophages to promote cancer progression. Int J Oncol 2020;56(1):151-64. DOI: 10.3892/ijo.2019.4933

46. Bohle A., Brandau S. Immune mechanisms in bacillus Calmette-Guerin immunotherapy for superficial bladder cancer. J Urol 2003;170(3):964-9. DOI: 10.1097/01.ju.0000073852.24341.4a

47. Redelman-Sidi G., Glickman M.S., Bochner B.H. The mechanism of action of BCG therapy for bladder cancer - a current perspective. Nat Rev Urol 2014;11(3):153-62. DOI: 10.1038/nrurol.2014.15

48. Ludwig A.T., Moore J.M., Luo Y. et al. Tumor necrosis factor-related apoptosis-inducing ligand: a novel mechanism for Bacillus Calmette-Guerin-induced antitumor activity. Cancer Res 2004;64(10):3386-90. DOI: 10.1158/0008-5472.CAN-04-0374

49. Yang G., Zhang L., Liu M. et al. CD163+ macrophages predict a poor prognosis in patients with primary T1 high-grade urothelial carcinoma of the bladder. World J Urol 2019;37(12):2721-6. DOI: 10.1007/s00345-018-02618-1

50. Bostrom M.M., Irjala H., Mirtti T. et al. Tumor-associated macrophages provide significant prognostic information in urothelial bladder cancer. PLoS One 2015;10(7):e0133552. DOI: 10.1371/journal.pone.0133552

51. Li P., Hao S., Ye Y. et al. Identification of an immune-related risk signature correlates with immunophenotype and predicts anti-PD-L1 efficacy of urothelial cancer. Front Cell Dev Biol 2021;9:646982. DOI: 10.3389/fcell.2021.646982

52. Xu Z., Wang L., Tian J. et al. High expression of B7-H3 and CD163 in cancer tissues indicates malignant clinicopathological status and poor prognosis of patients with urothelial cell carcinoma of the bladder. Oncol Lett 2018;15(5):6519-26. DOI: 10.3892/ol.2018.8173

53. Sjodahl G., Lovgren K., Lauss M. et al. Infiltration of CD3+ and CD68+ cells in bladder cancer is subtype specific and affects the outcome of patients with muscle-invasive tumors. Urol Oncol 2014;32(6):791-7. DOI: 10.1016/j.urolonc.2014.02.007

54. Wu S.Q., Xu R., Li X.F. et al. Prognostic roles of tumor associated macrophages in bladder cancer: a system review and meta-analysis. Oncotarget 2018;9(38):25294-303. DOI: 10.18632/oncotarget.25334

55. Maniecki M.B., Etzerodt A., Ulhoi B.P. et al. Tumor-promoting macrophages induce the expression of the macrophage-specific receptor CD163 in malignant cells. Int J Cancer 2012;131(10):2320-31. DOI: 10.1002/ijc.27506

56. Aljabery F., Olsson H., Gimm O. et al. M2-macrophage infiltration and macrophage traits of tumor cells in urinary bladder cancer. Urol Oncol 2018;36(4):159.e19-159.e26. DOI: 10.1016/j.urolonc.2017.11.020

57. Hanada T., Nakagawa M., Emoto A. et al. Prognostic value of tumor-associated macrophage count in human bladder cancer. Int J Urol 2000;7(7):263-9. DOI: 10.1046/j.1442-2042.2000.00190.x

58. Koga F., Kageyama Y., Kawakami S. et al. Prognostic significance of endothelial Per-Arnt-sim domain protein 1/hypoxia-inducible factor-2alpha expression in a subset of tumor associated macrophages in invasive bladder cancer. J Urol 2004;171(3):1080-4. DOI: 10.1097/01.ju.0000110541.62972.08

59. Asano T., Ohnishi K., Shiota T. et al. CD169-positive sinus macrophages in the lymph nodes determine bladder cancer prognosis. Cancer Sci 2018;109(5):1723-30. DOI: 10.1111/cas.13565