Pathomorphological Markers of Overcoming Radioresistance in the Treatment of Cervical Cancer

ORIGINAL ARTICLE
Pavel Yu. Andreev, Daniil Yu. Bugrimov, Andrey A. Filin, Olga V. Kashaeva, Natalya V. Korotkikh, Andrey A. Klimovich

 
International Journal of Biomedicine. 2020;10(2):120-123.
DOI: 10.21103/Article10(2)_OA6
Originally published June 15, 2020.

Abstract: 

The aim of this study was to study pathomorphological markers of decreasing radioresistance of cervical tumor tissue during radiation therapy and the administration of sodium deoxyribonucleate.
Methods and Results: The object of the study was patients with diagnosed cervical cancer (T1/FIGOIB, T1a1-2/FIGOIA1-2, and T1b1-2/FIGOIB1-2; NX0 and M0). All patients in the study were divided into 2 groups. The main group (MG) included 40 patients receiving combination of standard chemoradiotherapy with sodium deoxyribonucleate (5ml intramuscularly for 20 days). The comparison group (CG) included 23 patients receiving only standard chemoradiotherapy. Histological and immunohistochemical analysis was performed.
Conclusion: Against the background of complex therapy, the TLR9 expression indices in the patients of the MG were 24%-36% higher than the indices in the patients of the CG. The inclusion of sodium deoxyribonucleate—a TLR9 agonist—in the chemoradiotherapy regimen for cervical cancer has great potential for stimulating the TLR9 expression in immunocompetent cells of the tumor microenvironment.

Keywords: 
radioresistance • TLR9 expression • cervical cancer • pathomorphological markers
References: 
  1. Boyko AB, Demidova LV, Dubovetskaya OB, et al. Accompanying therapy for radiation treatment of female genital cancer. Proceedings of the First All-Russian Congress of RATRO “New Technologies in Radiation Therapy and Nuclear Medicine. Development Prospects ”(April 27–28, 2017, Sochi). - M .: KVAZAR, 2017; p. 27. [Abstract in Russian].
  2. Korotkikh NV, Moshurov IP, Klimovich AA, et al. The effect of Toll-like receptor 9 agonists on tumor expression of the immune control points PD1 and PDL-L1 in radiation therapy of squamous cervical cancer. The Third National Congress “Oncology of the reproductive organs: from prevention and early detection to effective treatment.” May 31 - June 2, 2018, Moscow.  Moscow, 2018; p. 49. [Abstract in Russian].
  3. Paauwe M, Heijkants RC, Oudt CH, van Pelt GW, Cui C, Theuer CP4, et al. Endoglin targeting inhibits tumor angiogenesis and metastatic spread in breast cancer. Oncogene. 2016 Aug 4;35(31):4069-79. doi: 10.1038/onc.2015.509.
  4. Zurkhaeva RZ, Saidov MZ. [Correlations between CD-positive cells and the expression of TLR-receptor when polypous rhinosinusitis]. Bulletin of Dagestan State Medical Academy. 2014;13(4):29-32.[Article in Russian].
  5. Martínez-Campos C, Burguete-García AI, Madrid-Marina V. Role of TLR9 in Oncogenic Virus-Produced Cancer. Viral Immunol. 2017 Mar;30(2):98-105. doi: 10.1089/vim.2016.0103.
  6. Chen X, Zhang Q, Luo Y, Gao C, Zhuang X, Xu G2, Qiao T. High-dose irradiation in combination with toll-like receptor 9 agonist CpG oligodeoxynucleotide 7909 downregulates PD-L1 expression via the NF-κB signaling pathway in non-small cell lung cancer cells. Onco Targets Ther. 2016 Oct 21;9:6511-6518. eCollection 2016. 
  7. Pasare C, Medzhitov R. Toll-like receptors: linking innate and adaptive immunity. Adv Exp Med Biol. 2005;560:11-8.
  8. Takeuchi O, Akira S. Pattern recognition receptors and inflammation. Cell. 2010 Mar 19;140(6):805-20. doi: 10.1016/j.cell.2010.01.022.
  9. Kawai T, Akira S. The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat Immunol. 2010 May;11(5):373-84. doi: 10.1038/ni.1863.
  10. Celhar T, Magalhães R, Fairhurst AM. TLR7 and TLR9 in SLE: when sensing self goes wrong. Immunol Res. 2012 Sep;53(1-3):58-77. doi: 10.1007/s12026-012-8270-1.
  11. Filatov OJ, Kashaev OV, Bugrimov DY, Klimovitch AA. Morphophysiological principles of immunological effect of eukaryotic DNA. Russian Journal of Immunology. 2013; 7/16(4): 385-390.[Article in Russian].
  12. Fujii T, Naing A, Rolfo C, Hajjar J. Biomarkers of response to immune checkpoint blockade in cancer treatment. Crit Rev Oncol Hematol. 2018 Oct;130:108-120. doi: 10.1016/j.critrevonc.2018.07.010.
  13. Huang X, Yang Y. Targeting the TLR9-MyD88 pathway in the regulation of adaptive immune responses. Expert Opin Ther Targets. 2010 Aug;14(8):787-96. doi: 10.1517/14728222.2010.501333.
  14. Filatov OYu, Kashaeva OV, Bugrimov DJu, Klimovich AA. [Morphophysiological principles of immunological effect of eukaryotic DNA]. Rossiiskii Immunologicheskii Zhurnal. 2013;7(4):385-90. [Article in Russian].
  15. Vollmer J, Weeratna RD, Jurk M, Samulowitz U, McCluskie MJ, Payette P, et al. Oligodeoxynucleotides lacking CpG dinucleotides mediate Toll-like receptor 9 dependent T helper type 2 biased immune stimulation. Immunology. 2004 Oct;113(2):212-23.

Download Article
Received April 3, 2020.
Accepted April 28, 2020.
©2020 International Medical Research and Development Corporation.