I.M. Voyeykova, N.L. Cheremshenko, A.V. Chumak, T.V. Symchych, О.М. Karaman, N.I. Fedosova

R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology of NAS of Ukraine, Kyiv, Ukraine


Summary. Aim:  to assess the effectiveness of the combined use of immune and chemotherapy with different metastatic tumors. Object and methods: two experimental models were used: Ehrlich adenocarcinoma (ACE) and Lewis lung carcinoma (CLL). As a means of chemotherapy used cisplatin, biotherapy – B. subtilis IMB B-7724 lectin, which in low concentrations has immunostimulating activity. Animals of different groups were introduced in mono-mode or theіr combination. The standard tumor growth and metastasis rates were evaluated. Upon completion of treatment, the activity of nonspecific immunity effectors was evaluated. The statistical analysis of the results was performed according to the generally accepted methods of variation statistics. Results: on both models of tumor growth, antitumor and antimetastatic efficacy is demonstrated as a means of immunotherapy of B. subtilis IMB B-7724 lectin. The severity of the effect depended on the mode of its introduction (mono-mode, combination with chemotherapy) and model tumors: for mice with ACE more effective was the introduction of lectin in mono-mode (the tumor growth index, TGI=53,2%); with LLC – combined injection of lectin and cisplatin (TGI =46,5%, metastasization inhibition index, МІІ=78,6%). The effect in both cases is associated with the ability of the lectin to remodel and maintain for a long time on the background of tumor growth polarization of macrophages in the direction of the proinflammatory state of M1 (increase in production of NO against the background of reduction of arginase activity (ARG)). This is evidenced by a strong positive correlation between NO/ARG and TGI level (r = 0.90, p <0.05 (ACE); also between NO/ARG and IIM level (r = 0.98, p <0.05 (CLL)). Conclusions: antitumor and antimetastatic efficiency of various regimens of use of chemo-/immunotherapy is due to the activation of nonspecific immune response and depends on both the immunogenic characteristics of tumors and on the initial physiological features of the immune system.

Keywords: Ehrlich adenocarcinoma, Lewis lung carcinoma, lectin, cisplatin, antitumor activity, antimetastatic activity



  1. Zitvogel L, Apetoh L, Ghiringhelli F, et al. Immunological aspects of cancer chemotherapy. Nat Rev Immunol 2008; 8: 59–73.
  2. Mian SA, AnjosAfonso F, Bonnet D. Advances in human immune system mouse models for studying human hematopoiesis and cancer immunotherapy. Front Immunol 2021; 11: 619236. doi: 10.3389/fimmu.2020.619236.
  3. Pai SY, Lurain K, Yarchoan R. How immunodeficiency can lead to malignancy. Hematology Am Soc Hematol Educ Program 2021; 2021 (1): 287–95. doi: 10.1182/hematology.2021000261.
  4. Moltó J, Moran T, Sirera G, Clotet B. Lung cancer in HIV-infected patients in the combination antiretroviral treatment era. Transl Lung Cancer Res 2015; 4 (6): 678–88. doi: 10.3978/j.issn.2218-6751.
  5. Casares N, Pequignot MO, Tesniere A, et al. Caspase-dependent immunogenicity of doxorubicin-induced tumor cell death. J Exp Med 2005; 202 (12): 1691–701. doi: 10.1084/jem.20050915.
  6. Merlano MC, Denaro N, Galizia D, et al. How chemotherapy affects the tumor immune microenvironment: a narrative review. Biomedicines 2022; 10 (8): 1822. doi: 10.3390/biomedicines10081822.
  7. Wu J, Waxman DJ. Immunogenic chemotherapy: Dose and schedule dependence and combination with immunotherapy. Cancer Lett 2018; 419: 210–21. doi: 10.1016/j.canlet.2018.01.050.
  8. Tesniere A, Schlemmer F, Boige V, et al. Immunogenic death of colon cancer cells treated with oxaliplatin. Oncogene 2010; 29: 482–91.
  9. Chen J, Huang X, Huang G, et al. Preconditioning chemotherapy with cisplatin enhances the antitumor activity of cytokine-induced killer cells in a murine melanoma model. Cancer Biother Radiopharm 2012; 27: 210–20.
  10. European Convention for the Protection of Vertebrate Animals used for Experimental and other Scientific Purposes ETS 123. Protection of Vertebrate Animals, 18.III.1986. 48.
  11. Kellar A, Egan C, Morris D. Preclinical murine models for lung cancer: clinical trial applications. Biomed Res Int 2015; 2015: 621324. doi: 10.1155/2015/621324.
  12. CalixtoCampos C, Zarpelon AC, Corrêa M, et al. The Ehrlich tumor induces pain-like behavior in mice: a novel model of cancer pain for pathophysiological studies and pharmacological screening. Biomed Res Int 2013; 2013: 624815. doi: 10.1155/2013/624815.
  13. Fedosova NI, Cheremshenko NL, Hetman KI, et al. Physicochemical and cytotoxicity properties of Bacillus subtilis ІМV В-7724 extracellular lectin. Mikrobiol Z 2021; 83 (1): 39–48.
  14. Chumak AB, Fedosova No, Cheremshenko NL, et al. Assessment of antitumor properties of lectin B.subtilis IMV B-7724 in studies in vivo. Oncology 2022; 24 (1): 31–6. doi: 10.32471/oncology.2663-7928.t-24-1-2022-g.10306.
  15. Chumak A, Fedosova N, Cheremshenko N, et al. Effect of lectin B.subtilis ІМV B-7724 on the activity of the effectors of cellular component of anticancer immunity. Exp Oncol 2023; 45 (3): 328–36.
  16. Symchych TV, Fedosova NI, Chumak AV, et al. Functions of tumor-associated macrophages and macrophages residing in remote anatomical niches in Ehrlich carcinoma bearing mice. Exp Oncol 2020; 42 (3): 197–203. doi: 10.32471/exp-oncology.2312-8852.vol-42-no-3.14928
  17. Anderson NR, Minutolo NG, Gill S, Klichinsky M. Macrophage-based approaches for cancer immunotherapy. Cancer Res 2021; 81: 1201–8. doi: 10.1158/0008-5472.CAN-20-2990.
  18. Yang Z, Guo J, Weng L, et al. Myeloid-derived suppressor cells-new and exciting players in lung cancer. J Hematol Oncol 2020; 13 (1): 10. doi: 10.1186/s13045-020-0843-1.
  19. Li F, Zhao Y, Wei L, et al. Tumor-infiltrating Treg, MDSC, and IDO expression associated with outcomes of neoadjuvant chemotherapy of breast cancer. Cancer Biol Ther 2018; 19 (8): 695–705. doi: 10.1080/15384047.2018.1450116.

No comments » Add comment