BIOLOGICAL MODEL OF LUNG CANCER COMBINATION AND TUBERCULOSIS: DEVELOPMENT FOR PRECLINICAL STUDY OF RATIONAL COMBINATIONS OF TARGETED ANTITUMOR AND ANTITUBERCULOSIS THERAPY

DOI: https://doi.org/10.29296/24999490-2024-02-04

Yu.S. Krylova1, 2, G.G. Kudriashov1, G.V. Tochilnikov3, T.I. Vinogradova1, M.A. Dokhov1, 4, P.K. Yablonskii1
1-Saint-Petersburg State Research Institute of Phthisiopulmonology of the Ministry of Healthcare of the Russian Federation,
Ligovsky av., 2–4, St. Petersburg, 191036, Russian Federation;
2-FGBOU VO «First St. Petersburg Statemedical university. acad. I.P. Pavlova» Ministry of Health of the Russian Federation,
st. Leo Tolstoy, 6–8, St. Petersburg, 197022, Russian Federation;
3-N.N. Petrov National Medicine Research Center of oncology,
Leningradskaya str., 68, village Pesochny, St. Petersburg, 197758, Russian Federation;
4-St. Petersburg State Pediatric Medical University, Ministry of Health of the Russian Federation,
st. Lithuanian, 2, St. Petersburg, 194100, Russian Federation;

Introduction. Lung cancer occupies a leading position in the structure of mortality from cancer. Chronic inflammation characteristic of tuberculosis increases the risk of lung cancer. Currently, more and more information is emerging confirming the cause-and-effect relationship between tuberculosis and cancer. The need to develop recommendations for public health regarding screening and treatment of tuberculosis in the tumor process determines the relevance of experimental studies on biological models of the combination of cancer and tuberculosis.. Aim. Creation а biological model of the combination of lung cancer and tuberculosis for preclinical study of rational combinations of antitumor and antituberculosis therapy. Material and methods: The biological model was implemented on C57BL/6 mice at the age of two months. Lewis epidermoid lung carcinoma was used to reproduce the tumor process. Modeling of tuberculosis was carried out using the reference strain Mycobacterium Tuberculosis H37RV. During the study, the following groups were formed: “intact mice” (healthy, uninfected with the Mycobacterium Tuberculosis (MBT) H37Rv strain without tumor cell transplantation); “control of MBT infection” (animals infected with Mycobacterium Tuberculosis strain H37Rv), “tumor control” (animals that were transplanted with epidermoid Lewis lung carcinoma) and “main group” (animals that were transplanted with epidermoid Lewis lung carcinoma simultaneously with MBT infection). Results. During the experiment, several models for creating the combined pathology of lung cancer and tuberculosis were identified. In the first (simultaneous infection and tumor inoculation), carcinoma developed more slowly in infected animals than in the tumor control group, and lung damage occurred with a predominance of the tuberculous process over the tumor process. The second (staged infection) also showed minimal metastatic manifestations with pronounced secondary changes in the primary tumor node. Analysis of the choice of model showed that the model with simultaneous infection and tumor inoculation most adequately ensures the development of the tumor process and tuberculosis infection, which allows maintaining the viability of the animal, fully developing the tumor process with metastasis to the lungs and obtaining the development of morphologically verified pulmonary tuberculosis.
Keywords: 
tuberculosis, lung cancer, choice of biological model of the tumor process and tuberculosis infection

Список литературы: 
  1. Bade B., Dela Cruz Ch Lung Cancer 2020: Epidemiology, Etiology, and Prevention Clin Chest Med. 2020; 41 (1): 1–24. DOI: 10.1016/j.ccm.2019.10.001
  2. Lee C.S., Shu C.C., Chen Y.C., Liao K.M., Ho C.H. Tuberculosis treatment incompletion in patients with lung cancer: occurrence and predictors. Int. J. Infect Dis. 2021; 113: 200–6. DOI: 10.1016/j.ijid.2021.09.072.
  3. Ardies C.M. Inflammation as cause for scar cancers of the lung. Integr Cancer Ther. 2003; 2 (3): 238–46. DOI: 10.1177/1534735403256332.
  4. Ho J.C., Leung C.C. Management of co-existent tuberculosis and lung cancer. Lung Cancer. 2018; 122: 83–7. DOI: 10.1016/j.lungcan.2018.05.030.
  5. Kim D.K., Lee S.W., Yoo C.G., Kim Y.W., Han S.K., Shim Y.S., Yim J.J. Clinical characteristics and treatment responses of tuberculosis in patients with malignancy receiving anticancer chemotherapy. Chest. 2005; 128 (4): 2218–22. DOI: 10.1378/chest.128.4.2218.
  6. Fujita K., Terashima T., Mio T. Anti-PD1 Antibody Treatment and the Development of Acute Pulmonary Tuberculosis. J. Thorac Oncol. 2016; 11 (12): 2238–40. DOI: 10.1016/j.jtho.2016.07.006.
  7. Dyck L., Mills K.H.G. Immune checkpoints and their inhibition in cancer and infectious diseases. Eur. J. Immunol. 2017; 47 (5): 765–79. DOI: 10.1002/eji.201646875.
  8. Cha S.I., Shin K.M., Lee J.W., Lee S.Y., Kim C.H., Park J.Y., Jung T.H. The clinical course of respiratory tuberculosis in lung cancer patients. Int. J. Tuberc Lung Dis. 2009; 13 (8): 1002–7.
  9. Состояние онкологической помощи населению России в 2019 году. Под ред. А.Д. Каприна, В.В. Старинского, А.О. Шахзадовой. М.: МНИОИ им. П.А. Герцена − филиал ФГБУ «НМИЦ радиологии» Минздрава России, 2020; 239. [The state of cancer care for the population of Russia in 2019 / Ed. HELL. Kaprina, V.V. Starinsky, A.O. Shakhzadova. M.: MNIOI im. P.A. Herzen – branch of the Federal State Budgetary Institution «National Medical Research Center of Radiology» of the Ministry of Health of Russia, 2020; 239 (in Russian)].
  10. Злокачественные новообразования в России в 2019 году (заболеваемость и смертность). Под ред. А.Д. Каприна, В.В. Старинского, А.О. Шахзадовой. М.: МНИОИ им. П.А. Герцена − филиал ФГБУ «НМИЦ радиологии» Минздрава России, 2020; 252. [Malignant neoplasms in Russia in 2019 (morbidity and mortality). Ed. HELL. Kaprina, V.V. Starinsky, A.O. Shakhzadova. M.: MNIOI im. P.A. Herzen – branch of the Federal State Budgetary Institution «National Medical Research Center of Radiology» of the Ministry of Health of Russia, 2020; 252 (in Russian)].
  11. Трякин А.А., Бесова Н. С., Волков Н. М. Практические рекомендации по общим принципам проведения противоопухолевой лекарственной терапии Злокачественные опухоли. 2022; 12 (3): 27–40. DOI 10.18027/2224-5057-2022-12-3s2-27-40. [Tryakin A.A., Besova N.S., Volkov N.M. Practical recommendations on the general principles of antitumor drug therapy Malignant tumors. 2022; 12 (3): 27–40 (in Russian)].
  12. Cocito C., Maes H. Immunological relatedness of the protective mechanisms against tuberculosis and cancer. Eur. J. Clin. Invest. 1998; 28 (1): 1–12. DOI: 10.1046/j.1365-2362.1998.00248.x
  13. Whitworth P.W., Pak C.C., Esgro J. Macrophages and cancer. Cancer Metast Rev 1990; 8: 319–51. https://doi.org/10.1007/BF00052607
  14. Norazmi M.N., Hohmann A.W., Skinner J.M., Jarvis L.R., Bradley J. Density and phenotype of tumour-associated mononuclear cells in colonic carcinomas determined by computer-assisted video image analysis. Immunology. 1990; 69 (2): 282–6.