CHANGES IN THE FUNCTIONAL ACTIVITY OF MACROPHAGES UNDER THE INFLUENCE OF BACTERIAL LECTIN APPLAIED IN DIFFERENT SCHEMES


N.I. Fedosova, A.V. Chumak, N.L. Cheremshenko, T.V. Symchych, О.М. Karaman, D.O. Karabaiev, I.M. Voyeykova
R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology of NAS of Ukraine, Kyiv, Ukraine

DOI: https://doi.org/10.15407/oncology.2023.01.032

 

 Aim: to investigate the antitumor effect and the influence of B. subtilis IMV B-7724 lectin applied as a single therapy or in combination with cisplatin on various manifestations of macrophages functional activity during the growth of a metastasizing experimental tumor. Materials and methods: the study was performed on C57Bl/6J mice bearing Lewis lung carcinoma (LLC). The effect of the lectin applied as a single therapy or in combination with cisplatin on tumor growth and the functional activity of peritoneal macrophages were evaluated. The functional activity of peritoneal macrophages was studied by the level of NO production, arginase and cytotoxic activity. Results: there was demonstrated an antimetastatic efficacy of B. subtilis IMV B-7724 lectin applied in Lewis lung carcinoma model either as a single therapy or in combination with cisplatin. In all probability, this effect was grounded by the changes in macrophages functional activity. As it is evidenced by a significant (p < 0.05) suppression of macrophages’ cytotoxic activity and characteristic changes in arginase metabolism, M2 macrophages predominated in the control (untreated) tumor-bearing mice. The features of L-arginine metabolism and cytotoxic activity in peritoneal macrophages indicate the preservation of their antitumor activity (polarization toward M1 type) at the terminal stage of experimental tumor growth. Conclusions: in the animals bearing experimental tumor, the most pronounced antitumor effect was observed when the bacterial lectin was applied in combination with cisplatin. The use of B. subtilis IMV B-7724 lectin as a therapeutic agent (either as a single therapy or in combination with cisplatin) preserved the antitumor activity of macrophages and promoted their polarization toward M1 direction at the terminal stage of tumor growth.

Keywords: macrophages, M1 and M2 polarization, functional activity, Lewis lung carcinoma, B. subtilis IMV B-7724 lectin, cisplatin

 

References

  1. Baxter-Holland M, Dass Doxorubicin, mesenchymal stem cell toxicity and antitumour activity: implications for clinical use. J Pharm Pharmacol 2018; 70 (3): 320–7.
  2. Wu J, Waxman Immunogenic chemotherapy: Dose and schedule dependence and combination with immunotherapy. Cancer Lett 2018; 419: 210–221. doi: 10.1016/j.canlet.2018.01.050.
  3. Galluzzi L, Buqué A, Kepp O, et al. Immunological effof conventional chemotherapy and targeted anticancer agents. Cancer Cell 2015; 28 (6): 690–714. doi: 10.1016/j. ccell.2015.10.012.
  4. Rodrigues MC, Morais JAV, Ganassin R, et al. An over- view on immunogenic cell death in cancer biology and Pharmaceutics 2022; 14 (8): 1564. doi: 10.3390/ pharmaceutics14081564.
  5. Ramakrishnan R, Assudani D, Nagaraj S, et al. Chemo- therapy enhances tumor cell susceptibility to CTL-mediated killing during cancer immunotherapy in J Clin Invest 2010; 120 (4): 1111–24. doi: 10.1172/JCI40269.
  6. Zhang L, Zhou C, Zhang S, et al. Chemotherapy reinforces anti-tumor immune response and enhances clinical efficacy of immune checkpoint Front Oncol 2022; 12: 939249. doi: 10.3389/fonc.2022.939249.
  7. Merlano MC, Denaro N, Galizia D, et al. How chemo- therapy affects the tumor immune microenvironment: a narrative review. Biomedicines 2022; 10 (8): 1 doi: 10. 3390/biomedicines10081822.
  8. Zheng X, Mansouri S, Krager A, et al. Metabolism in tu- mour-associated macrophages: a quid pro quo with the tumour Eur Respir Rev 2020; 29 (157): 200134. doi: 10.1183/16000617.0134-2020.
  9. Xu Y, Wang X, Liu L, et al. Role of macrophages in tumor progression and therapy (Review). Int J Oncol 2022; 60 (5): 5 doi: 10.3892/ij 47.
  10. Lin Y, Xu J, Lan Tumor-associated macrophages in tumor metastasis: biological roles and clinical therapeutic ap- plications. J Hematol Oncol 2019; 12 (1): 76. doi: 10.1186/ s13045-019-0760-3.
  11. Jackute J, Zemaitis M, Pranys D, et al. Distribution of M1 and M2 macrophages in tumor islets and stroma in relation to prognosis of non-small cell lung cancer. BMC Immunol 2018; 19 (1): doi: 10.1186/s12865-018-0241-4.
  12. Wei X, Nie S, Liu H, et al. Angiopoietin-like protein 2 facili- tates non-small cell lung cancer progression by promoting the polarization of M2 tumor-associated macrophages. Am J Cancer Res 2017; 7 (11): 2220–33.
  13. Pitt JM, Marabelle A, Eggermont A, et al. Targeting the tu- mor microenvironment: removing obstruction to anticancer immune responses and immunotherapy. Ann Oncol 2016; 27 (8): 1482–92. doi: 11093/annonc/mdw168.
  14. Kozhemyakin YM, Khromov OS, Filonenko MA, Sayfutdi- nova HA. Guideline on management of laboratory ani- mals and work with Kyiv: Avitsena, 2002. 179 p. (in Ukrainian)
  15. Kellar A, Egan C, Morris preclinical murine models for lung cancer: clinical trial applications. Biomed Res Int 2015; 2015: 621324. doi: 10.1155/2015/621324.
  16. Fedosova NI, Cheremshenko NL, Hetman KI, et al. Phy- sicochemical and cytotoxicity properties of Bacillus sub- tilis ІМV В-7724 extracellular Mikrobiol Z 2021; 83 (1): 39–48. https://doi.org/10.15407/microbiolj83.01. 039.
  17. Reiner NE. Methods in molecular Macrophages and dendritic cells. Methods and protocols. Preface. Me- thods Mol Biol 2009; 531: v-vi. doi: 10.1007/978-1-59745- 396-7.
  18. Van de Loosdrecht AA, Beelen RH, Ossenkoppele GJ, et al. A tetrazolium-based colorimetric MTT assay to quantitate human monocyte mediated cytotoxicity against leukemic cells from cell lines and patients with acute myeloid leuke- J Immunol Met 1994; 174 (1–2): 311–20.
  19. Chumak AV, Fedosova NI, Cheremshenko NL, et al. Macro- phage polarization in dynamics of Lewis lung carcinoma growth and metastasis. Exp Oncol 2021; 43 (1): 15–20. doi: 10.32471/exp-oncology.2312-8852.vol-43-no-1.15829.
  20. Yoshida C, Kadota K, Ikeda T, et al. Tumor-associated macrophage infiltration is associated with a higher rate of tumor spread through air spaces in resected lung adeno- c Lung Cancer 2021; 158: 91–6. doi: 10.1016/j. lungcan.2021.06.009.
  21. Rajtak A, Ostrowska-Leśko M, Żak K, et al. Integration of local and systemic immunity in ovarian cancer: Implications for immunotherapy. Front Immunol 2022; 13: 101 doi: 10.3389/fi 1018256.
  22. Almeida-Nunes DL, Mendes-Frias A, Silvestre R, et al. Immune tumor microenvironment in ovarian cancer as- c Int J Mol Sci 2022; 23 (18): 10692. doi: 10.3390/ ij  31810692.
  23. Pe KCS, Saetung R, Yodsurang V, et al. Triple-negative breast cancer influences a mixed M1/M2 macrophage phenotype associated with tumor PLoS One 2022; 17 (8): e0273044. doi: 10.1371/journal.pone.0273044.
  24. Redente EF, Dwyer-Nield LD, Merrick DT, et al. Tumor progression stage and anatomical site regulate tumor-as- sociated macrophage and bone marrow-derived monocyte Am J Pathol 2010; 176 (6): 2972–85. doi: 10.2353/ajpath.2010.090879.
  25. Sumitomo R, Hirai T, Fujita M, et al. M2 tumor-associated macrophages promote tumor progression in non-small- cell lung Exp Ther Med 2019; 18 (6): 4490–8. doi: 10.3892/etm.2019.8068.
  26. Cao L, Che X, Qiu X, et al. M2 macrophage infiltration into tumor islets leads to poor prognosis in non-small-cell lung cancer. Cancer Manag Res 2019; 11: 6125–38. doi: 12147/ CMAR.S199832.
  27. Mei J, Xiao Z, Guo C, et al. Prognostic impact of tumor- associated macrophage infiltration in non-small cell lung cancer: a systemic review and meta-analysis. Oncotar- get 2016; 7 (23): 34217–28. doi: 118632/oncotarget. 9079.

No comments » Add comment