PROSPECTS FOR USING THE PHENOMENON OF MACROPHAGES PLASTICITY TO EVALUATE THE EFFICIENCY OF CANCER THERAPY
DOI:
https://doi.org/10.32471/oncology.2663-7928.t-22-1-2020-g.8830Keywords:
carcinosarcoma Walker 256, chemotherapy, immunotherapy, M1 and M2 macrophagesAbstract
Objectives: determination of indicators of the functional activity of peritoneal macrophages: rats with Walker-256 carcinosarcoma under various regimens of antitumor therapy and assessment of the participation of macrophages in the implementation of the antitumor effect. Object and methods: the study was conducted in Wistar rats. Walker 256 carcinosarcoma was used as a tumor growth model. For the treatment of animals doxorubicin or cisplatin were used both in monotherapy and in combined regimens with the xenogeneic antitumor vaccine (XAV). The XAV was prepared according to the method on the basis of antigens of chicken embryonic tissue and protein-containing metabolite of B. subtilis 7025 with molecular mass 70 kDa. The characteristics of tumor growth and functional activity of peritoneal macrophages were evaluated on day 24. Results: according to tumor growth characteristics, the most effective was the combined application of XAV + doxorubicin. The animals of this group were characterized by a decrease in tumor size comparing with XAV group (by 4.4 times, p < 0.05), XAV + cisplatin) (by 1.9 times). On day 24 of the tumor growth in non-treated animals, type M2 macrophages predominated; chemotherapy and/or immunotherapy led to increase of type M1 macrophages that was supported by a significant increase in nitric oxide (NO) production and a decrease in arginase activity. The most effective was the combination XAV + doxorubicin: NO level increased by 1.6 and arginase activity decreased by 1.5 times (p < 0.05 for both parameters compared with XAV group). Cisplatin application both in monotherapy, and in the combination with XAV did not exert the similar effect. Conclusions: the most pronounced antitumor efficacy in Walker 256 carcinosarcoma model was seen at application of the combined chemotherapy and immunotherapy (regimen XAV + doxorubicin). This effect was probably due to a significant increase in the amount of of type M1 macrophages, which exhibit antitumor properties. The strong negative correlation between tumor size and macrophages functional activity with the M1 phenotype indicates a significant role for these cells in inhibiting tumor growth.
References
Andersen MH, Sorensen RB, Schrama D, et al. Cancer treatment: the combination of vaccination with other therapies. Cancer Immunol Immunother 2008; 57: 1735–43.
Menard C, Martin F, Apetoh L, et al. Cancer chemotherapy: not only a direct cytotoxic effect, but also an adjuvant for antitumor immunity. Cancer Immunol Immunother 2008; 57: 1579–87.
Riley RS, June CH, Langer R, Mitchell MJ. Delivery technologies for cancer immunotherapy. Nat Rev Drug Discov 2019; 18 (3): 175–96.
Ventola CL. Cancer immunotherapy. Part 2: efficacy, safety, and other clinical considerations. P&T 2017; 42 (7): 452–63.
Apetoh L, Vegran F, Ladoire S, Ghiringhelli F. Restoration of antitumor immunity through selective inhibition of myeloid derived suppressor cells by anticancer therapies. Curr Mol Med 2011; 11: 365–72.
Apetoh L, Ladoire S, Coukos G, Ghiringhelli F. Combining immunotherapy and anticancer agents. Ann Oncol 2015; 26(9): 1813–23.
Schlom J, Arlen PM, Gulley JL. Cancer vaccines: moving beyond current paradigms. Clin Cancer Res 2007; 13: 3776–82.
Wheeler CJ, Das A, Liu G, et al. Clinical responsiveness of glioblastoma multiforme to chemotherapy after vaccination. Clin Cancer Res 2004; 10: 5316–26.
García-Aranda M, Redondo M. Immunotherapy: a challenge of breast cancer treatment. Cancers (Basel) 2019; 11 (12): 1822.
Mina LA, Lim S, Bahadur SW, Firoz AT. Immunotherapy for the treatment of breast cancer: emerging new data. Breast Cancer (Dove Med Press) 2019; 11: 321–8.
Luhong Yang, Yanxia Wang, Huafeng Wang. Use of immunotherapy in the treatment of gastric cancer. Oncol Lett 2019; 18 (6): 5681–90.
Corrales L, Scilla K, Caglevic C, et al. Immunotherapy in lung cancer: a new age in cancer treatment. Adv Exp Med Biol 2018; 995: 65–95.
Verovkina NO. Recent advances in immunotherapy in the treatment of cancer patients: the use of immunotherapy in non-small cell lung cancer. Clin oncol 2018; 8 (4): 228–31. (in Ukrainian)
Ganesh O, Stadler K, Cercek ZK, et al. Immunotherapy in colorectal cancer: rationale, challenges and potential. Nat Rev Gastroenterol Hepatol 2019; 16: 361–75.
Tintelnot J, Stein A. Immunotherapy in colorectal cancer: available clinical evidence, challenges and novel approaches. World J Gastroenterol 2019; 25(29): 3920–8.
Ott PA, Hu Z, Keskin DB, et al. An immunogenic personal neoantigen vaccine for patients with melanoma. Nature 2017; 547: 217–21.
Symchych TV, Fedosova NI, Karaman ОМ, et al. Anticancer effect and immunologic response to xenogeneic embryonic proteins in mice bearing Ehrlich solid carcinoma. Exp Oncol 2017; 39 (1): 42–8.
Symchych TV, Fedosova NI, Karaman ОМ, et al. The effects of early postoperative immunization with xenogeneic embryo proteins on Lewis lung carcinoma model. Exp Oncol 2018; 40 (4): 275–81.
Fedosova NI, Voeykova IM, Karaman OM, et al. Cytotoxic activity of immune cells following administration of xenogeneic cancer vaccine in mice with melanoma B-16. Exp Oncol 2015; 37 (2): 130–4.
Kraśko J, Zilionytė K, Darinskas A, et al. Post-operative unadjuvanted therapeutic xenovaccination with chicken whole embryo vaccine suppresses distant micrometastases and prolongs survival in a murine Lewis lung carcinoma model. Oncology Letters 2018; 15: 5098–104.
Aparecida do Amaral L, Santos MR, Oliveira de Souza GH. Walker-256 tumor: experimental model, implantation sites and number of cells for ascitic and solid tumor development. Brazilian Archives Biology and Technology 2019; 62 (12): e19180284.
Potebnya GP, Bolyukh IA, Didenko GV, et al. Method of designing antitumor vaccine. (Pat. № 77647 UA). Publ. 27.08.2013. Bul. №16. (in Ukrainian).
Kiseleva EP, Polevschikov AV. The method of automated accounting of the NST test. Clin Lab Diagn 1994; 4: 27–9. (in Russian).
Enzyme-linked immunosorbent assay: Ngo T,. Lenhoff G (eds). M.: Mir, 1988. 446 p. (in Russian).
Macrophages and dendritic cells. Methods and Protocols. Neil E. Reiner (eds). NY: Humana Press, 2009. 368 p.
Shugaley VS, Kozina AS. Urea content and arginase activity in rat organs during acclimatization to cold. Fiziol journal USSR 1977; 8: 1199–202. (in Russian).
Sidenko AB, Vishnyakov VV, Isaev SM. Theory of statistics. М.: MAX-Press; 2011. 343 p. (in Russian).
Zajciuk VV, Vereshchako RI, Cheshuk VE, et al. Efficacy of combination of anticancer autovaccine with standard anticancer treatment in breast cancer (analysis of 10-year surveillance data). Oncology 2015; 17(1): 47–54. (in Russian).
Weagel E, Smith C, Liu PG, et al. Macrophage polarization and its role in cancer. J Clin Cell Immunol 2015; 6: 338. doi:10.4172/2155–9899.1000338
Zhao C, Mirando AC, Sove RJ, et al. A mechanistic integrativecomputational model of macrophage polarization: Implications in human pathophysiology. PLoSComput Biol 2019; 15(11): e1007468. https://doi.org/10.1371/journal. pcbi.1007468
