tumorsMalignant tumoursMalignant tumours2224-50572587-6813Rosoncoweb10.18027/2224-5057-2022-2-3s1-3-8tumors-994Research ArticleСтатьиСостав и фенотип опухолевой стромы как маркер прогноза заболеванияКовалеваО. В.

Москва

ovkovaleva@gmail.comПодлеснаяП. А.

Москва

ПетренкоА. А.

Москва

ГрачевА. Н.

Москва

ФГБУ «НМИЦ онкологии им. Н. Н. Блохина» Минздрава РоссииRussian Federation202218112022123s138Copyright © Ковалева О.В., Подлесная П.А., Петренко А.А., Грачев А.Н., 20222022Ковалева О.В., Подлесная П.А., Петренко А.А., Грачев А.Н.Ковалева О.В., Подлесная П.А., Петренко А.А., Грачев А.Н.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.malignanttumors.org/jour/article/view/994

Рассматривая микроокружение опухоли, исследователи отмечают большое количество типов клеток, его составляющих. Изучаются различные типы клеток, начиная от стромальных фибробластов и клеток иммунной системы, заканчивая эндотелиальными клетками и адипоцитами. Однако, несмотря на большое количество исследований, использование не стандартизированных маркеров стромальных клеток и подходов в оценке прогноза заболевания до сих пор не привели к их использованию в рутинной клинической практике. Для многих солидных опухолей неотъемлемой составляющей опухолевой стромы является резидентный микробиом, способный в значительной степени повлиять на характер активации иммунокомпетентных клеток микроокружения и анализ состава которого, на сегодняшний день также предлагается использовать в качестве прогностического маркера. В настоящем обзоре литературы проанализирована информация по микробиому и клеточному составу и фенотипу иммунологической составляющей опухолевой стромы новообразований легкого, механизмам их взаимодействия и влиянию этого взаимодействия на прогрессию опухоли. А также изучена возможность их использования для оценки прогноза заболевания и в качестве мишеней для терапии.

микробиомстромаопухольпрогнозИсследование выполнено за счет гранта Российского научного фонда № 22-15-00291, https://rscf.ru/project/22-15-00291.ReferencesStout R. D., Suttles J. Functional plasticity [of] macrophages: reversible adaptation to changing microenvironments. JLeukocBiol. 2004 ; 76 (3) : 509–13.Stout R. D., Suttles J. Functional plasticity [of] macrophages: reversible adaptation to changing microenvironments. JLeukocBiol. 2004 ; 76 (3) : 509–13.Gratchev A., Kzhyshkowska J., Kothe K., Muller-Molinet I., Kannookadan S., Utikal J., Goerdt S. Mphi1 and Mphi2 can be re-polarized by Th2 or Th1 cytokines, respectively, and respond to exogenous danger signals. Immunobiology. 2006 ; 211 (6–8) : 473–86. https://doi.org/10.1016/j.imbio.2006.05.017.Gratchev A., Kzhyshkowska J., Kothe K., Muller-Molinet I., Kannookadan S., Utikal J., Goerdt S. Mphi1 and Mphi2 can be re-polarized by Th2 or Th1 cytokines, respectively, and respond to exogenous danger signals. Immunobiology. 2006 ; 211 (6–8) : 473–86. https://doi.org/10.1016/j.imbio.2006.05.017.Locati M., Mantovani A., Sica A. Macrophage activation and polarization as an adaptive component of innate immunity. Advances in immunology. 2013 ; 120 : 163–84. https://doi.org/10.1016/B978-0-12-417028-5.00006–5.Locati M., Mantovani A., Sica A. Macrophage activation and polarization as an adaptive component of innate immunity. Advances in immunology. 2013 ; 120 : 163–84. https://doi.org/10.1016/B978-0-12-417028-5.00006–5.Gratchev A., Schledzewski K., Guillot P., Goerdt S. Alternatively activated antigen-presenting cells: molecular repertoire, immune regulation, and healing. Skin pharmacology and applied skin physiology. 2001 ; 14 (5) : 272–9. https://doi.org/56357.Gratchev A., Schledzewski K., Guillot P., Goerdt S. Alternatively activated antigen-presenting cells: molecular repertoire, immune regulation, and healing. Skin pharmacology and applied skin physiology. 2001 ; 14 (5) : 272–9. https://doi.org/56357.Goerdt S., Orfanos C. E. Other functions, other genes: alternative activation of antigen- presenting cells. Immunity. 1999 ; 10 (2) : 137–42.Goerdt S., Orfanos C. E. Other functions, other genes: alternative activation of antigen- presenting cells. Immunity. 1999 ; 10 (2) : 137–42.Mei J., Xiao Z., Guo C., Pu Q., Ma L., Liu C., Lin F., Liao H., You Z., Liu L. Prognostic impact of tumor-associated macrophage infiltration in non-small cell lung cancer: A systemic review and meta-analysis. Oncotarget. 2016 ; 7 (23) : 34217–28. https://doi.org/10.18632/oncotarget.9079.Mei J., Xiao Z., Guo C., Pu Q., Ma L., Liu C., Lin F., Liao H., You Z., Liu L. Prognostic impact of tumor-associated macrophage infiltration in non-small cell lung cancer: A systemic review and meta-analysis. Oncotarget. 2016 ; 7 (23) : 34217–28. https://doi.org/10.18632/oncotarget.9079.Holness C. L., Simmons D. L. Molecular cloning of CD68, a human macrophage marker related to lysosomal glycoproteins. Blood. 1993 ; 81 (6) : 1607–13.Holness C. L., Simmons D. L. Molecular cloning of CD68, a human macrophage marker related to lysosomal glycoproteins. Blood. 1993 ; 81 (6) : 1607–13.Leek R. D., Lewis C. E., Whitehouse R., Greenall M., Clarke J., Harris A. L. Association of macrophage infiltration with angiogenesis and prognosis in invasive breast carcinoma. Cancer Res. 1996 ; 56 (20) : 4625–9.Leek R. D., Lewis C. E., Whitehouse R., Greenall M., Clarke J., Harris A. L. Association of macrophage infiltration with angiogenesis and prognosis in invasive breast carcinoma. Cancer Res. 1996 ; 56 (20) : 4625–9.Yang L., Wang F., Wang L., Huang L., Wang J., Zhang B., Zhang Y. CD163+ tumor-associated macrophage is a prognostic biomarker and is associated with therapeutic effect on malignant pleural effusion of lung cancer patients. Oncotarget. 2015 ; 6 (12) : 10592–603. https://doi.org/10.18632/oncotarget.3547.Yang L., Wang F., Wang L., Huang L., Wang J., Zhang B., Zhang Y. CD163+ tumor-associated macrophage is a prognostic biomarker and is associated with therapeutic effect on malignant pleural effusion of lung cancer patients. Oncotarget. 2015 ; 6 (12) : 10592–603. https://doi.org/10.18632/oncotarget.3547.Gao J., Ren Y., Guo H., Mao R., Xie H., Su H., She Y., Deng J., Yang M., Han B., et al. A new method for predicting survival in stage I non-small cell lung cancer patients: nomogram based on macrophage immunoscore, TNM stage and lymphocyte-to-monocyte ratio. Ann Transl Med. 2020 ; 8 (7) : 470. https://doi.org/10.21037/atm.2020.03.113.Gao J., Ren Y., Guo H., Mao R., Xie H., Su H., She Y., Deng J., Yang M., Han B., et al. A new method for predicting survival in stage I non-small cell lung cancer patients: nomogram based on macrophage immunoscore, TNM stage and lymphocyte-to-monocyte ratio. Ann Transl Med. 2020 ; 8 (7) : 470. https://doi.org/10.21037/atm.2020.03.113.Sumitomo R., Hirai T., Fujita M., Murakami H., Otake Y., Huang C. L. M2 tumor-associated macrophages promote tumor progression in non-small-cell lung cancer. Experimental and therapeutic medicine. 2019 ; 18 (6) : 4490–8. https://doi.org/10.3892/etm.2019.8068.Sumitomo R., Hirai T., Fujita M., Murakami H., Otake Y., Huang C. L. M2 tumor-associated macrophages promote tumor progression in non-small-cell lung cancer. Experimental and therapeutic medicine. 2019 ; 18 (6) : 4490–8. https://doi.org/10.3892/etm.2019.8068.Shen J., Sun X., Pan B., Cao S., Cao J., Che D., Liu F., Zhang S., Yu Y. IL-17 induces macrophages to M2-like phenotype via NF-kappaB. Cancer Manag Res. 2018 ; 10 : 4217–28. https://doi.org/10.2147/CMAR.S174899.Shen J., Sun X., Pan B., Cao S., Cao J., Che D., Liu F., Zhang S., Yu Y. IL-17 induces macrophages to M2-like phenotype via NF-kappaB. Cancer Manag Res. 2018 ; 10 : 4217–28. https://doi.org/10.2147/CMAR.S174899.Jackute J., Zemaitis M., Pranys D., Sitkauskiene B., Miliauskas S., Vaitkiene S., Sakalauskas R. Distribution of M1 and M2 macrophages in tumor islets and stroma in relation to prognosis of non-small cell lung cancer. BMC immunology. 2018 ; 19 (1) : 3. https://doi.org/10.1186/s12865-018-0241-4.Jackute J., Zemaitis M., Pranys D., Sitkauskiene B., Miliauskas S., Vaitkiene S., Sakalauskas R. Distribution of M1 and M2 macrophages in tumor islets and stroma in relation to prognosis of non-small cell lung cancer. BMC immunology. 2018 ; 19 (1) : 3. https://doi.org/10.1186/s12865-018-0241-4.Antonia S. J., Extermann M., Flavell R. A. Immunologic nonresponsiveness to tumors. Crit Rev Oncog. 1998 ; 9 (1) : 35–41. https://doi.org/10.1615/critrevoncog.v9.i1.30.Antonia S. J., Extermann M., Flavell R. A. Immunologic nonresponsiveness to tumors. Crit Rev Oncog. 1998 ; 9 (1) : 35–41. https://doi.org/10.1615/critrevoncog.v9.i1.30.He C., Qiao H., Jiang H., Sun X. The inhibitory role of b7-h4 in antitumor immunity: association with cancer progression and survival. Clinical & developmental immunology. 2011 ; 2011 : 695834. https://doi.org/10.1155/2011/695834.He C., Qiao H., Jiang H., Sun X. The inhibitory role of b7-h4 in antitumor immunity: association with cancer progression and survival. Clinical & developmental immunology. 2011 ; 2011 : 695834. https://doi.org/10.1155/2011/695834.Hurkmans D. P., Kuipers M. E., Smit J., van Marion R., Mathijssen R. H. J., Postmus P. E., Hiemstra P. S., Aerts J., von der Thusen J. H., van der Burg S. H. Tumor mutational load, CD8 (+) T cells, expression of PD-L1 and HLA class I to guide immunotherapy decisions in NSCLC patients. Cancer immunology, immunotherapy : CII. 2020 ; 69 (5) : 771–7. https://doi.org/10.1007/s00262-020-02506-x.Hurkmans D. P., Kuipers M. E., Smit J., van Marion R., Mathijssen R. H. J., Postmus P. E., Hiemstra P. S., Aerts J., von der Thusen J. H., van der Burg S. H. Tumor mutational load, CD8 (+) T cells, expression of PD-L1 and HLA class I to guide immunotherapy decisions in NSCLC patients. Cancer immunology, immunotherapy : CII. 2020 ; 69 (5) : 771–7. https://doi.org/10.1007/s00262-020-02506-x.Emens L. A., Cruz C., Eder J. P., Braiteh F., Chung C., Tolaney S. M., Kuter I., Nanda R., Cassier P. A., Delord J. P., et al. Long-term Clinical Outcomes and Biomarker Analyses of Atezolizumab Therapy for Patients With Metastatic Triple-Negative Breast Cancer: A Phase 1 Study. JAMA Oncol. 2019 ; 5 (1) : 74–82. https://doi.org/10.1001/jamaoncol.2018.4224.Emens L. A., Cruz C., Eder J. P., Braiteh F., Chung C., Tolaney S. M., Kuter I., Nanda R., Cassier P. A., Delord J. P., et al. Long-term Clinical Outcomes and Biomarker Analyses of Atezolizumab Therapy for Patients With Metastatic Triple-Negative Breast Cancer: A Phase 1 Study. JAMA Oncol. 2019 ; 5 (1) : 74–82. https://doi.org/10.1001/jamaoncol.2018.4224.Schubert L. A., Jeffery E., Zhang Y., Ramsdell F., Ziegler S. F. Scurfin (FOXP3) acts as a repressor of transcription and regulates T cell activation. J Biol Chem. 2001 ; 276 (40) : 37672–9. https://doi.org/10.1074/jbc.M104521200.Schubert L. A., Jeffery E., Zhang Y., Ramsdell F., Ziegler S. F. Scurfin (FOXP3) acts as a repressor of transcription and regulates T cell activation. J Biol Chem. 2001 ; 276 (40) : 37672–9. https://doi.org/10.1074/jbc.M104521200.Fontenot J. D., Gavin M. A., Rudensky A. Y. Foxp3 programs the development and function of CD4+ CD25+ regulatory T cells. Nature immunology. 2003 ; 4 (4) : 330–6. https://doi.org/10.1038/ni904.Fontenot J. D., Gavin M. A., Rudensky A. Y. Foxp3 programs the development and function of CD4+ CD25+ regulatory T cells. Nature immunology. 2003 ; 4 (4) : 330–6. https://doi.org/10.1038/ni904.Hori S., Nomura T., Sakaguchi S. Control of regulatory T cell development by the transcription factor Foxp3. Science. 2003 ; 299 (5609) : 1057–61. https://doi.org/10.1126/science.1079490.Hori S., Nomura T., Sakaguchi S. Control of regulatory T cell development by the transcription factor Foxp3. Science. 2003 ; 299 (5609) : 1057–61. https://doi.org/10.1126/science.1079490.Sakaguchi S., Mikami N., Wing J. B., Tanaka A., Ichiyama K., Ohkura N. Regulatory T Cells and Human Disease. Annu Rev Immunol. 2020 ; 38 : 541–66. https://doi.org/10.1146/annurev-immunol-042718–041717.Sakaguchi S., Mikami N., Wing J. B., Tanaka A., Ichiyama K., Ohkura N. Regulatory T Cells and Human Disease. Annu Rev Immunol. 2020 ; 38 : 541–66. https://doi.org/10.1146/annurev-immunol-042718–041717.Sakaguchi S . Naturally arising Foxp3- expressing CD25+ CD4+ regulatory T cells in immunological tolerance to self and non-self. NatImmunol. 2005 ; 6 (4) : 345–52.Sakaguchi S . Naturally arising Foxp3- expressing CD25+ CD4+ regulatory T cells in immunological tolerance to self and non-self. NatImmunol. 2005 ; 6 (4) : 345–52.Scotta C., Soligo M., Camperio C., Piccolella E. FOXP3 induced by CD28 / B7 interaction regulates CD25 and anergic phenotype in human CD4+ CD25- T lymphocytes. Journal of immunology. 2008 ; 181 (2) : 1025–33. https://doi.org/10.4049/jimmunol.181.2.1025.Scotta C., Soligo M., Camperio C., Piccolella E. FOXP3 induced by CD28 / B7 interaction regulates CD25 and anergic phenotype in human CD4+ CD25- T lymphocytes. Journal of immunology. 2008 ; 181 (2) : 1025–33. https://doi.org/10.4049/jimmunol.181.2.1025.Facciabene A., Peng X., Hagemann I. S., Balint K., Barchetti A., Wang L. P., Gimotty P. A., Gilks C. B., Lal P., Zhang L., et al. Tumour hypoxia promotes tolerance and angiogenesis via CCL28 and T (reg) cells. Nature. 2011 ; 475 (7355) : 226–30. https://doi.org/10.1038/nature10169.Facciabene A., Peng X., Hagemann I. S., Balint K., Barchetti A., Wang L. P., Gimotty P. A., Gilks C. B., Lal P., Zhang L., et al. Tumour hypoxia promotes tolerance and angiogenesis via CCL28 and T (reg) cells. Nature. 2011 ; 475 (7355) : 226–30. https://doi.org/10.1038/nature10169.Tao H., Mimura Y., Aoe K., Kobayashi S., Yamamoto H., Matsuda E., Okabe K., Matsumoto T., Sugi K., Ueoka H. Prognostic potential of FOXP3 expression in non-small cell lung cancer cells combined with tumor-infiltrating regulatory T cells. Lung Cancer. 2012 ; 75 (1) : 95–101. https://doi.org/10.1016/j.lungcan.2011.06.002.Tao H., Mimura Y., Aoe K., Kobayashi S., Yamamoto H., Matsuda E., Okabe K., Matsumoto T., Sugi K., Ueoka H. Prognostic potential of FOXP3 expression in non-small cell lung cancer cells combined with tumor-infiltrating regulatory T cells. Lung Cancer. 2012 ; 75 (1) : 95–101. https://doi.org/10.1016/j.lungcan.2011.06.002.Shimizu K., Nakata M., Hirami Y., Yukawa T., Maeda A., Tanemoto K. Tumor-infiltrating Foxp3+ regulatory T cells are correlated with cyclooxygenase-2 expression and are associated with recurrence in resected non-small cell lung cancer. J Thorac Oncol. 2010 ; 5 (5) : 585–90. https://doi.org/10.1097/JTO.0b013e3181d60fd7.Shimizu K., Nakata M., Hirami Y., Yukawa T., Maeda A., Tanemoto K. Tumor-infiltrating Foxp3+ regulatory T cells are correlated with cyclooxygenase-2 expression and are associated with recurrence in resected non-small cell lung cancer. J Thorac Oncol. 2010 ; 5 (5) : 585–90. https://doi.org/10.1097/JTO.0b013e3181d60fd7.Shang B., Liu Y., Jiang S. J., Liu Y. Prognostic value of tumor-infiltrating FoxP3+ regulatory T cells in cancers: a systematic review and meta-analysis. Scientific reports. 2015 ; 5 : 15179. https://doi.org/10.1038/srep15179.Shang B., Liu Y., Jiang S. J., Liu Y. Prognostic value of tumor-infiltrating FoxP3+ regulatory T cells in cancers: a systematic review and meta-analysis. Scientific reports. 2015 ; 5 : 15179. https://doi.org/10.1038/srep15179.Marsigliante S., Biscozzo L., Marra A., Nicolardi G., Leo G., Lobreglio G. B., Storelli C. Computerised counting of tumour infiltrating lymphocytes in 90 breast cancer specimens. Cancer letters. 1999 ; 139 (1) : 33–41. https://doi.org/10.1016/s0304–3835(98)00379–6.Marsigliante S., Biscozzo L., Marra A., Nicolardi G., Leo G., Lobreglio G. B., Storelli C. Computerised counting of tumour infiltrating lymphocytes in 90 breast cancer specimens. Cancer letters. 1999 ; 139 (1) : 33–41. https://doi.org/10.1016/s0304–3835(98)00379–6.Petitprez F., de Reynies A., Keung E. Z., Chen T. W., Sun C. M., Calderaro J., Jeng Y. M., Hsiao L. P., Lacroix L., Bougouin A., et al. B cells are associated with survival and immunotherapy response in sarcoma. Nature. 2020 ; 577 (7791) : 556–60. https:// doi.org/10.1038/s41586-019-1906-8.Petitprez F., de Reynies A., Keung E. Z., Chen T. W., Sun C. M., Calderaro J., Jeng Y. M., Hsiao L. P., Lacroix L., Bougouin A., et al. B cells are associated with survival and immunotherapy response in sarcoma. Nature. 2020 ; 577 (7791) : 556–60. https:// doi.org/10.1038/s41586-019-1906-8.Mahmoud S. M., Lee A. H., Paish E. C., Macmillan R. D., Ellis I. O., Green A. R. The prognostic significance of B lymphocytes in invasive carcinoma of the breast. Breast Cancer Res Treat. 2012 ; 132 (2) : 545–53. https://doi.org/10.1007/s10549-011-1620-1.Mahmoud S. M., Lee A. H., Paish E. C., Macmillan R. D., Ellis I. O., Green A. R. The prognostic significance of B lymphocytes in invasive carcinoma of the breast. Breast Cancer Res Treat. 2012 ; 132 (2) : 545–53. https://doi.org/10.1007/s10549-011-1620-1.Edin S., Kaprio T., Hagstrom J., Larsson P., Mustonen H., Bockelman C., Strigard K., Gunnarsson U., Haglund C., Palmqvist R. The Prognostic Importance of CD20 (+) B lymphocytes in Colorectal Cancer and the Relation to Other Immune Cell subsets. Scientific reports. 2019 ; 9 (1) : 19997. https://doi.org/10.1038/s41598-019-56441-8.Edin S., Kaprio T., Hagstrom J., Larsson P., Mustonen H., Bockelman C., Strigard K., Gunnarsson U., Haglund C., Palmqvist R. The Prognostic Importance of CD20 (+) B lymphocytes in Colorectal Cancer and the Relation to Other Immune Cell subsets. Scientific reports. 2019 ; 9 (1) : 19997. https://doi.org/10.1038/s41598-019-56441-8.Germain C., Gnjatic S., Tamzalit F., Knockaert S., Remark R., Goc J., Lepelley A., Becht E., Katsahian S., Bizouard G., et al. Presence of B cells in tertiary lymphoid structures is associated with a protective immunity in patients with lung cancer. American journal of respiratory and critical care medicine. 2014 ; 189 (7) : 832–44. https://doi.org/10.1164/rccm.201309–1611OC.Germain C., Gnjatic S., Tamzalit F., Knockaert S., Remark R., Goc J., Lepelley A., Becht E., Katsahian S., Bizouard G., et al. Presence of B cells in tertiary lymphoid structures is associated with a protective immunity in patients with lung cancer. American journal of respiratory and critical care medicine. 2014 ; 189 (7) : 832–44. https://doi.org/10.1164/rccm.201309–1611OC.Santoiemma P. P., Reyes C., Wang L. P., McLane M. W., Feldman M. D., Tanyi J. L., Powell D. J., Jr. Systematic evaluation of multiple immune markers reveals prognostic factors in ovarian cancer. Gynecol Oncol. 2016 ; 143 (1) : 120–7. https://doi.org/10.1016/j.ygyno.2016.07.105.Santoiemma P. P., Reyes C., Wang L. P., McLane M. W., Feldman M. D., Tanyi J. L., Powell D. J., Jr. Systematic evaluation of multiple immune markers reveals prognostic factors in ovarian cancer. Gynecol Oncol. 2016 ; 143 (1) : 120–7. https://doi.org/10.1016/j.ygyno.2016.07.105.Garg K., Maurer M., Griss J., Bruggen M. C., Wolf I. H., Wagner C., Willi N., Mertz K. D., Wagner S. N. Tumor-associated B cells in cutaneous primary melanoma and improved clinical outcome. Human pathology. 2016 ; 54 : 157–64. https://doi.org/10.1016/j.humpath.2016.03.022.Garg K., Maurer M., Griss J., Bruggen M. C., Wolf I. H., Wagner C., Willi N., Mertz K. D., Wagner S. N. Tumor-associated B cells in cutaneous primary melanoma and improved clinical outcome. Human pathology. 2016 ; 54 : 157–64. https://doi.org/10.1016/j.humpath.2016.03.022.Nathan C., Xie Q. W. Nitric oxide synthases: roles, tolls, and controls. Cell. 1994 ; 78 (6) : 915–8. https://doi.org/10.1016/0092–8674(94)90266–6.Nathan C., Xie Q. W. Nitric oxide synthases: roles, tolls, and controls. Cell. 1994 ; 78 (6) : 915–8. https://doi.org/10.1016/0092–8674(94)90266–6.Garrido P., Shalaby A., Walsh E. M., Keane N., Webber M., Keane M. M., Sullivan F. J., Kerin M. J., Callagy G., Ryan A. E., et al. Impact of inducible nitric oxide synthase (iNOS) expression on triple negative breast cancer outcome and activation of EGFR and ERK signaling pathways. Oncotarget. 2017 ; 8 (46) : 80568–88. https://doi.org/10.18632/oncotarget.19631.Garrido P., Shalaby A., Walsh E. M., Keane N., Webber M., Keane M. M., Sullivan F. J., Kerin M. J., Callagy G., Ryan A. E., et al. Impact of inducible nitric oxide synthase (iNOS) expression on triple negative breast cancer outcome and activation of EGFR and ERK signaling pathways. Oncotarget. 2017 ; 8 (46) : 80568–88. https://doi.org/10.18632/oncotarget.19631.Chen C. N., Hsieh F. J., Cheng Y. M., Chang K. J., Lee P. H. Expression of inducible nitric oxide synthase and cyclooxygenase-2 in angiogenesis and clinical outcome of human gastric cancer. Journal of surgical oncology. 2006 ; 94 (3) : 226–33. https://doi.org/10.1002/jso.20372.Chen C. N., Hsieh F. J., Cheng Y. M., Chang K. J., Lee P. H. Expression of inducible nitric oxide synthase and cyclooxygenase-2 in angiogenesis and clinical outcome of human gastric cancer. Journal of surgical oncology. 2006 ; 94 (3) : 226–33. https://doi.org/10.1002/jso.20372.Raspollini M. R., Amunni G., Villanucci A., Boddi V., Baroni G., Taddei A., Taddei G. L. Expression of inducible nitric oxide synthase and cyclooxygenase-2 in ovarian cancer: correlation with clinical outcome. Gynecol Oncol. 2004 ; 92 (3) : 806–12. https://doi.org/10.1016/j.ygyno.2003.12.023.Raspollini M. R., Amunni G., Villanucci A., Boddi V., Baroni G., Taddei A., Taddei G. L. Expression of inducible nitric oxide synthase and cyclooxygenase-2 in ovarian cancer: correlation with clinical outcome. Gynecol Oncol. 2004 ; 92 (3) : 806–12. https://doi.org/10.1016/j.ygyno.2003.12.023.Puhakka A., Kinnula V., Napankangas U., Saily M., Koistinen P., Paakko P., Soini Y. High expression of nitric oxide synthases is a favorable prognostic sign in non-small cell lung carcinoma. APMIS: acta pathologica, microbiologica, et immunologica Scandinavica. 2003 ; 111 (12) : 1137–46. https://doi.org/10.1111/j.1600–0463.2003.apm1111210.x.Puhakka A., Kinnula V., Napankangas U., Saily M., Koistinen P., Paakko P., Soini Y. High expression of nitric oxide synthases is a favorable prognostic sign in non-small cell lung carcinoma. APMIS: acta pathologica, microbiologica, et immunologica Scandinavica. 2003 ; 111 (12) : 1137–46. https://doi.org/10.1111/j.1600–0463.2003.apm1111210.x.Kovaleva O. V., Rashidova M. A., Samoilova D. V., Podlesnaya P. A., Tabiev R. M., Mochalnikova V. V., Gratchev A. CHID1 Is a Novel Prognostic Marker of Non-Small Cell Lung Cancer. International journal of molecular sciences. 2021 ; 22 (1). https://doi.org/10.3390/ijms22010450.Kovaleva O. V., Rashidova M. A., Samoilova D. V., Podlesnaya P. A., Tabiev R. M., Mochalnikova V. V., Gratchev A. CHID1 Is a Novel Prognostic Marker of Non-Small Cell Lung Cancer. International journal of molecular sciences. 2021 ; 22 (1). https://doi.org/10.3390/ijms22010450.Dong Q., Chen E. S., Zhao C., Jin C. Host-Microbiome Interaction in Lung Cancer. Front Immunol. 2021 ; 12 : 679829. https://doi.org/10.3389/fimmu.2021.679829.Dong Q., Chen E. S., Zhao C., Jin C. Host-Microbiome Interaction in Lung Cancer. Front Immunol. 2021 ; 12 : 679829. https://doi.org/10.3389/fimmu.2021.679829.Erb-Downward J. R., Thompson D. L., Han M. K., Freeman C. M., McCloskey L., Schmidt L. A., Young V. B., Toews G. B., Curtis J. L., Sundaram B., et al. Analysis of the lung microbiome in the «healthy» smoker and in COPD. PloS one. 2011 ; 6 (2) : e16384. https://doi.org/10.1371/journal.pone.0016384.Erb-Downward J. R., Thompson D. L., Han M. K., Freeman C. M., McCloskey L., Schmidt L. A., Young V. B., Toews G. B., Curtis J. L., Sundaram B., et al. Analysis of the lung microbiome in the «healthy» smoker and in COPD. PloS one. 2011 ; 6 (2) : e16384. https://doi.org/10.1371/journal.pone.0016384.Hilty M., Burke C., Pedro H., Cardenas P., Bush A., Bossley C., Davies J., Ervine A., Poulter L., Pachter L., et al. Disordered microbial communities in asthmatic airways. PloS one. 2010 ; 5 (1) : e8578. https://doi.org/10.1371/journal.pone.0008578.Hilty M., Burke C., Pedro H., Cardenas P., Bush A., Bossley C., Davies J., Ervine A., Poulter L., Pachter L., et al. Disordered microbial communities in asthmatic airways. PloS one. 2010 ; 5 (1) : e8578. https://doi.org/10.1371/journal.pone.0008578.Beck J. M., Young V. B., Huffnagle G. B. The microbiome of the lung. Translational research: the journal of laboratory and clinical medicine. 2012 ; 160 (4) : 258–66. https://doi.org/10.1016/j.trsl.2012.02.005.Beck J. M., Young V. B., Huffnagle G. B. The microbiome of the lung. Translational research: the journal of laboratory and clinical medicine. 2012 ; 160 (4) : 258–66. https://doi.org/10.1016/j.trsl.2012.02.005.Laroumagne S., Salinas-Pineda A., Hermant C., Murris M., Gourraud P. A., Do C., Segonds C., Didier A., Mazieres J. [Incidence and characteristics of bronchial colonisation in patient with lung cancer: a retrospective study of 388 cases]. Rev Mal Respir. 2011 ; 28 (3) : 328–35. https://doi.org/10.1016/j.rmr.2010.05.020.Laroumagne S., Salinas-Pineda A., Hermant C., Murris M., Gourraud P. A., Do C., Segonds C., Didier A., Mazieres J. [Incidence and characteristics of bronchial colonisation in patient with lung cancer: a retrospective study of 388 cases]. Rev Mal Respir. 2011 ; 28 (3) : 328–35. https://doi.org/10.1016/j.rmr.2010.05.020.Hosgood H. D., 3rd, Sapkota A. R., Rothman N., Rohan T., Hu W., Xu J., Vermeulen R., He X., White J. R., Wu G., et al. The potential role of lung microbiota in lung cancer attributed to household coal burning exposures. Environ Mol Mutagen. 2014 ; 55 (8) : 643–51. https://doi.org/10.1002/em.21878.Hosgood H. D., 3rd, Sapkota A. R., Rothman N., Rohan T., Hu W., Xu J., Vermeulen R., He X., White J. R., Wu G., et al. The potential role of lung microbiota in lung cancer attributed to household coal burning exposures. Environ Mol Mutagen. 2014 ; 55 (8) : 643–51. https://doi.org/10.1002/em.21878.Yu G., Gail M. H., Consonni D., Carugno M., Humphrys M., Pesatori A. C., Caporaso N. E., Goedert J. J., Ravel J., Landi M. T. Characterizing human lung tissue microbiota and its relationship to epidemiological and clinical features. Genome biology. 2016 ; 17 (1) : 163. https://doi.org/10.1186/s13059-016-1021-1.Yu G., Gail M. H., Consonni D., Carugno M., Humphrys M., Pesatori A. C., Caporaso N. E., Goedert J. J., Ravel J., Landi M. T. Characterizing human lung tissue microbiota and its relationship to epidemiological and clinical features. Genome biology. 2016 ; 17 (1) : 163. https://doi.org/10.1186/s13059-016-1021-1.Wong J. L., Evans S. E. Bacterial Pneumonia in Patients with Cancer: Novel Risk Factors and Management. Clin Chest Med. 2017 ; 38 (2) : 263–77. https://doi.org/10.1016/j.ccm.2016.12.005.Wong J. L., Evans S. E. Bacterial Pneumonia in Patients with Cancer: Novel Risk Factors and Management. Clin Chest Med. 2017 ; 38 (2) : 263–77. https://doi.org/10.1016/j.ccm.2016.12.005.Liu H. X., Tao L. L., Zhang J., Zhu Y. G., Zheng Y., Liu D., Zhou M., Ke H., Shi M. M., Qu J. M. Difference of lower airway microbiome in bilateral protected specimen brush between lung cancer patients with unilateral lobar masses and control subjects. International journal of cancer Journal international du cancer. 2018 ; 142 (4) : 769–78. https://doi.org/10.1002/ijc.31098.Liu H. X., Tao L. L., Zhang J., Zhu Y. G., Zheng Y., Liu D., Zhou M., Ke H., Shi M. M., Qu J. M. Difference of lower airway microbiome in bilateral protected specimen brush between lung cancer patients with unilateral lobar masses and control subjects. International journal of cancer Journal international du cancer. 2018 ; 142 (4) : 769–78. https://doi.org/10.1002/ijc.31098.Greathouse K. L., White J. R., Vargas A. J., Bliskovsky V. V., Beck J. A., von Muhlinen N., Polley E. C., Bowman E. D., Khan M. A., Robles A. I., et al. Interaction between the microbiome and TP53 in human lung cancer. Genome biology. 2018 ; 19 (1) : 123. https://doi.org/10.1186/s13059-018-1501-6.Greathouse K. L., White J. R., Vargas A. J., Bliskovsky V. V., Beck J. A., von Muhlinen N., Polley E. C., Bowman E. D., Khan M. A., Robles A. I., et al. Interaction between the microbiome and TP53 in human lung cancer. Genome biology. 2018 ; 19 (1) : 123. https://doi.org/10.1186/s13059-018-1501-6.Yan X., Yang M., Liu J., Gao R., Hu J., Li J., Zhang L., Shi Y., Guo H., Cheng J., et al. Discovery and validation of potential bacterial biomarkers for lung cancer. American journal of cancer research. 2015 ; 5 (10) : 3111–22.Yan X., Yang M., Liu J., Gao R., Hu J., Li J., Zhang L., Shi Y., Guo H., Cheng J., et al. Discovery and validation of potential bacterial biomarkers for lung cancer. American journal of cancer research. 2015 ; 5 (10) : 3111–22.Liu Y., O’Brien J. L., Ajami N. J., Scheurer M. E., Amirian E. S., Armstrong G., Tsavachidis S., Thrift A. P., Jiao L., Wong M. C., et al. Lung tissue microbial profile in lung cancer is distinct from emphysema. American journal of cancer research. 2018 ; 8 (9) : 1775–87.Liu Y., O’Brien J. L., Ajami N. J., Scheurer M. E., Amirian E. S., Armstrong G., Tsavachidis S., Thrift A. P., Jiao L., Wong M. C., et al. Lung tissue microbial profile in lung cancer is distinct from emphysema. American journal of cancer research. 2018 ; 8 (9) : 1775–87.Riquelme E., Zhang Y., Zhang L., Montiel M., Zoltan M., Dong W., Quesada P., Sahin I., Chandra V., San Lucas A., et al. Tumor Microbiome Diversity and Composition Influence Pancreatic Cancer Outcomes. Cell. 2019 ; 178 (4) : 795–806 e12. https://doi.org/10.1016/j.cell.2019.07.008.Riquelme E., Zhang Y., Zhang L., Montiel M., Zoltan M., Dong W., Quesada P., Sahin I., Chandra V., San Lucas A., et al. Tumor Microbiome Diversity and Composition Influence Pancreatic Cancer Outcomes. Cell. 2019 ; 178 (4) : 795–806 e12. https://doi.org/10.1016/j.cell.2019.07.008.Kovaleva O., Podlesnaya P., Rashidova M., Samoilova D., Petrenko A., Zborovskaya I., Mochalnikova V., Kataev V., Khlopko Y., Plotnikov A., et al. Lung Microbiome Differentially Impacts Survival of Patients with Non-Small Cell Lung Cancer Depending on Tumor Stroma Phenotype. Biomedicines. 2020 ; 8 (9). https://doi.org/10.3390/biomedicines8090349.Kovaleva O., Podlesnaya P., Rashidova M., Samoilova D., Petrenko A., Zborovskaya I., Mochalnikova V., Kataev V., Khlopko Y., Plotnikov A., et al. Lung Microbiome Differentially Impacts Survival of Patients with Non-Small Cell Lung Cancer Depending on Tumor Stroma Phenotype. Biomedicines. 2020 ; 8 (9). https://doi.org/10.3390/biomedicines8090349.Kovaleva O. V., Podlesnaya P., Sorokin M., Mochalnikova V., Kataev V., Khlopko Y. A., Plotnikov A. O., Stilidi I. S., Kushlinskii N. E., Gratchev A. Macrophage Phenotype in Combination with Tumor Microbiome Composition Predicts RCC Patients’ Survival: A Pilot Study. Biomedicines. 2022 ; 10 (7). https://doi.org/10.3390/biomedicines10071516.Kovaleva O. V., Podlesnaya P., Sorokin M., Mochalnikova V., Kataev V., Khlopko Y. A., Plotnikov A. O., Stilidi I. S., Kushlinskii N. E., Gratchev A. Macrophage Phenotype in Combination with Tumor Microbiome Composition Predicts RCC Patients’ Survival: A Pilot Study. Biomedicines. 2022 ; 10 (7). https://doi.org/10.3390/biomedicines10071516.Kovaleva O., Podlesnaya P., Rashidova M., Samoilova D., Petrenko A., Mochalnikova V., Kataev V., Khlopko Y., Plotnikov A., Gratchev A. Prognostic Significance of the Microbiome and Stromal Cells Phenotype in Esophagus Squamous Cell Carcinoma. Biomedicines. 2021 ; 9 (7). https://doi.org/10.3390/biomedicines9070743.Kovaleva O., Podlesnaya P., Rashidova M., Samoilova D., Petrenko A., Mochalnikova V., Kataev V., Khlopko Y., Plotnikov A., Gratchev A. Prognostic Significance of the Microbiome and Stromal Cells Phenotype in Esophagus Squamous Cell Carcinoma. Biomedicines. 2021 ; 9 (7). https://doi.org/10.3390/biomedicines9070743.Jain T., Sharma P., Are A. C., Vickers S. M., Dudeja V. New Insights Into the Cancer-Microbiome-Immune Axis: Decrypting a Decade of Discoveries. Front Immunol. 2021 ; 12 : 622064. https://doi.org/10.3389/fimmu.2021.622064.Jain T., Sharma P., Are A. C., Vickers S. M., Dudeja V. New Insights Into the Cancer-Microbiome-Immune Axis: Decrypting a Decade of Discoveries. Front Immunol. 2021 ; 12 : 622064. https://doi.org/10.3389/fimmu.2021.622064.

The authors declare that there are no conflicts of interest present.