Preview

Innovative Medicine of Kuban

Advanced search

Comparative analysis of some immunological parameters depending on the tumor location on the right and left sides of colon

https://doi.org/10.35401/2541-9897-2022-25-3-20-28

Abstract

Background: Colorectal cancer is now an urgent problem in oncology. Recently, specialists have been interested in a comparative analysis of differences in the clinical course of malignant tumors in the proximal and distal colon. The sections differ not only in their embryogenesis and sources of blood supply, but also in the clinical course and population and epidemiological characteristics. The issue of distinctive immunological characteristics of tumors of the colon depending on the location remains open.

Objective: A comparative analysis of local subpopulations of immunocompetent cells and an assessment of number of cells with the CD45+/- phenotype expressing toll-like receptors (TLRs) depending on the tumor location on the right or left sides of the colon.

Material and methods: The study included 50 patients with verified colon cancer. The majority of patients were females – 26 (52%), aged 67 ± 0.4 years, and 50% of patients with stage II disease. Depending on the tumor location (the right or left sides of the colon), the patients were divided into 2 groups of 25 people each. All patients underwent standard surgery at the initial stage. The obtained material was used for subsequent studies: a cell suspension was obtained from a tumor tissue fragment, the perifocal zone (1–3 cm from the tumor) which was processed using an antibody panel (Becton Dickinson, USA) to identify the main subpopulations of leukocytes and lymphocytes. Expression of TLRs (2, 3, 4, 8, 9) on CD45+, CD45- cell populations was also determined using the BD FACSCanto flow cytometer (Becton Dickinson, USA). Statistical processing of the results was performed using the STATISTICA 13.3 package (StatSoft Inc., USA).

Results: A comparative analysis of immunological parameters, depending on the tumor location on the right or left sides of the colon, showed:

  1. Tissues of the right-sided tumors had a higher T-lymphocytic infiltration, compared to the left-sided tumors, while the latter showed a higher B-lymphocytic infiltration (p = 0.025).
  2. Peritumoral zone tissues of left-sided tumors demonstrated a decrease of lymphocytes levels (p = 0.027), NKT – (p = 0.035), NK – (p = 0.041) and В lymphocytes (p = 0.038), and a significant increase in CD8+- (p = 0.02) and DP cells (p = 0.0018).
  3. Left-sided tumors showed a percentage decrease of CD45- cells expressing TLR4 and TLR8, compared to right-sided tumors, by 38% (p = 0.038) and 25% (p = 0.043).
  4. There was a decrease in the number of CD45+ cells expressing TLR2 and TLR4 in left-sided tumors by 54% (p = 0.035) and 33% (p = 0.04) respectively, than in right-sided tumors.
  5. The percent of CD45- cells expressing TLR4 in the perifocal tissues of left-sided tumors decreased by 61% (p = 0.031) in comparison to the corresponding tissues in right-sided tumors.
  6. The numbers of CD45+ cells expressing TLR2 and TLR4 were 81% (p = 0.02) and 87% (p = 0.018) lower respectively in the peritumoral tissues of left-sided tumors, compared to the corresponding tissues in right-sided tumors.

Conclusion: The revealed characteristics of the local subpopulations of immunocompetent cells and the numbers of CD45+/- cells expressing TLRs depending on the tumor location on the right or left sides of the colon can serve as a prognosis of the disease clinical course and the choice of further treatment tactics.

About the Authors

O. I. Kit
National Medical Research Centre for Oncology
Russian Federation

Oleg I. Kit - Dr. Sci. (Med.), Professor, Academician of the Russian Academy of Sciences, General Director.

Rostov-on-Don



E. A. Dzhenkova
National Medical Research Centre for Oncology
Russian Federation

Elena A. Dzhenkova - Dr. Sci. (Bio.), Associate Professor, Scientific Secretary of the Academic Council.

Rostov-on-Don



E. A. Mirzoyan
National Medical Research Centre for Oncology
Russian Federation

Ellada A. Mirzoyan - Postgraduate Student.

63, 14th str., Rostov-on-Don, 344037

 



A. B. Sagakyants
National Medical Research Centre for Oncology
Russian Federation

Alexander B. Sagakyants - Cand. Sci. (Bio.), Associate Professor, Head of Laboratory of Immunophenotyping of Tumors.

Rostov-on-Don



E. Yu. Zlatnik
National Medical Research Centre for Oncology
Russian Federation

Elena Yu. Zlatnik - Dr. Sci. (Med.), Professor, Chief researcher, Laboratory of Immunophenotyping of Tumors.

Rostov-on-Don



E. S. Bondarenko
National Medical Research Centre for Oncology
Russian Federation

Elena S. Bondarenko - Junior researcher, Laboratory of Immunophenotyping of Tumors.

Rostov-on-Don



I. A. Novikova
National Medical Research Centre for Oncology
Russian Federation

Inna A. Novikova - Cand. Sci. (Med.), Deputy General Director for Science.

Rostov-on-Don



A. A. Maslov
National Medical Research Centre for Oncology
Russian Federation

Andrey A. Maslov - Dr. Sci. (Med.), Professor, Chief Physician.

Rostov-onDon



References

1. Kit OI. Issue of colorectal cancer at the beginning of 21 century: achievements and prospects. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2013;3(23):65–71. (In Russ.).

2. Kit OI, Dzhenkova EA, Mirzoyan EA, et al. Molecular genetic classification of colorectal cancer subtypes: current state of the problem. South Russian Journal of Cancer. 2021;2(2):50–56. (In Russ.). https://doi.org/10.37748/2686-9039-2021-2-2-6

3. Maratkyzy M, Kabildina NA, Beisenayeva AR, et al. Epidemiological aspects of colorectal cancer. Medicine and ecology. 2020;2(95):15–20. (In Russ.)

4. Kaprin AD, Starinsky VV, Shakhzadova AO. Malignant neoplasms in Russia in 2020 (morbidity and mortality). Moscow: National Medical Research Center of Radiology of the Russian Ministry of Health; 2021:252. (In Russ.).

5. Kit OI, Dzhenkova EA, Mirzoyan EA, et al. Characteristics of local cellular immunity in colon cancer depending on tumor location. Modern Problems of Science and Education. 2022;3. (In Russ.). https://doi.org/10.17513/spno.31695

6. Fedyanin MYu, Tryakin AA, Tjulandin SA. Localization of the primary tumor of the colon: are there essential differences? Pelvic Surgery and Oncology. 2017;7(3):35−48. (In Russ.). https://doi.org/10.17650/2220-3478-2017-7-3-35-48

7. Benedix F, Schmidt U, Mroczkowski P, et al. Colon carcinoma – classification into right and left sided cancer or according to colonic subsite? Analysis of 29,568 patients. Eur J Surg Oncolс. 2011;37(2):134–139. PMID: 21193285. https://doi.org/10.1016/j.ejso.2010.12.004

8. Davydov MI, Gantsev ShKh. Oncology: textbook. Moscow: GEOTAR-Media; 2020:920. (In Russ.).

9. Sears CL, Geis AL, Housseau F. Bacteroides fragilis subverts mucosal biology: from symbiont to colon carcinogenesis. J Clin Invest. 2014;124(10):4166–4172. PMID: 25105360. PMCID: PMC4191034. https://doi.org/10.1172/JCI72334

10. LaPointe LC, Dunne R, Brown GS, et al. Map of differential transcript expression in the normal human large intestine. Physiol Genomics. 2008;33(1):50–64. PMID: 18056783. https://doi.org/10.1152/physiolgenomics.00185.2006

11. Sagakyants AB. United immunological forum: current trends in the development of fundamental and applied oncoimmunology (Novosibirsk, 2019). South Russian Journal of Cancer. 2020;1(2):36– 45. (In Russ.). https://doi.org/10.37748/2687-0533-2020-1-2-5

12. Schreiber RD. Cancer immunoediting: integrating immunity’s roles in cancer suppression and promotion. Science. 2011;331:1565–1570. PMID: 21436444. https://doi.org/10.1126/science.1203486

13. Väyrynen JP, Tuomisto A, Klintrup K, et al. Detailed analysis of inflammatory cell infiltration in colorectal cancer. British Journal of Cancer. 2013;109:1839–1847. PMID: 24008661. PMCID: PMC3790164. https://doi.org/10.1038/bjc.2013.508

14. Kit OI, Frantsiyants EM, Nikipelova EA, et al. Changes in markers of proliferation, neoangiogenesis and plasminogen activation system in rectal cancer tissue. Experimental and Clinical Gastroenterology. 2015;114(2):40–45. (In Russ.).

15. Tabiasco J, Devêvre E, Rufer N, et al. Human effector CD8+T lymphocytes express TLR3 as a functional coreceptor. Journal of immunology. 2006;177(12):8708–8713. PMID: 17142772. https://doi.org/10.4049/jimmunol.177.12.8708

16. Li TT, Ogino S, Qian ZR. Toll-like receptor signaling in colorectal cancer: carcinogenesis to cancer therapy. World journal of gastroenterology. 2014;20(47):17699–17708. PMID: 25548469. PMCID: PMC4273121. https://doi.org/10.3748/wjg.v20.i47.17699

17. Svitich OA, Filina AB, Davydova NV, et al. The role of innate immunity factors in tumorigenesis process. Medical Immunology (Russia). 2018;20(2):151–162. (In Russ.) https://doi.org/10.15789/1563-0625-2018-2-151-162

18. Pages F, Galon J, Fridman WH. The essential role of the in situ immune reaction in human colorectal cancer. Jornal of Leukocyte Biology. 2008;84(4):981–987. PMID: 18559950. https://doi.org/10.1189/jlb.1107773

19. Grizzi F, Bianchi P, Malesci A, et al. Prognostic value of innate and adaptive immunity in colorectal cancer. World Journal of Gastroenterology. 2013;19(2):174–184. PMID: 23345940. PMCID: PMC3547568. https://doi.org/10.3748/wjg.v19.i2.174

20. Mei Z, Liu Y, Liu C, et al. Tumor-infiltrating inflammation and prornosis in colorectal cancer: systematic review and meta-analysis. British Journal of Cancer. 2014;110(6):1595–1605. PMID: 24504370. PMCID: PMC3960618. https://doi.org/10.1038/bjc.2014.46

21. Chiba T, Ohtani H, Mizoi T, et al. Intraepithelial CD8+ T-cell-count becomes a prognostic factor after a longer followup period in human colorectal carcinoma: possible association with suppression of micrometastasis. British Journal of Cancer. 2004;91(9):1711–1717. PMID: 15494715. PMCID: PMC2410024. https://doi.org/10.1038/sj.bjc.6602201

22. Nosho K, Baba Y, Tanaka N, et al. Tumour-infiltrating T-cell subsets, molecular changes in colorectal cancer, and prognosis: cohort study and literature review. Journal of Pathology. 2010;222(4):350–366. PMID: 20927778. PMCID: PMC3033700. https://doi.org/10.1002/path.2774

23. Masayuki F, Yasmin H, Daisy C, et al. Innate immune signaling by Toll-like receptor-4 (TLR4) shapes the inflammatory microenvironment in colitisassociated tumors. Inflammatory Bowel Diseases. 2009;15(7):997–1006. PMID: 19229991. PMCID: PMC2712657. https://doi.org/10.1002/ibd.20880

24. Garaude J, Kent A, van Rooijen N, et al. Simultaneous targeting of toll- and nod-like receptors induces effective tumorspecific immune responses. Science Translational Medicine. 2012;4(120):120ra16. PMID: 22323829. https://doi.org/10.1126/scitranslmed.3002868

25. Wang EL, Qian ZR, Nakasono M, et al. High expression of Toll-like receptor 4/myeloid differentiation factor 88 signals correlates with poor prognosis in colorectal cancer. British journal of cancer. 2010;102(5):908–915. PMID: 20145615. PMCID: PMC2833250. https://doi.org/10.1038/sj.bjc.6605558

26. Kantola T, Klintrup K, Väyrynen JP, et al. Stage-dependent alterations of the serum cytokine pattern in colorectal carcinoma. British journal of cancer. 2012;107(10):1729–1736. PMID: 23059742. PMCID: PMC3493870. https://doi.org/10.1038/bjc.2012.456

27. Tye H, Jenkins BJ. Tying the knot between cytokine and toll-like receptor signaling in gastrointestinal tract cancers. Cancer science. 2013;104(9):1139–1145. PMID: 23710764. PMCID: PMC7656558. https://doi.org/10.1111/cas.12205

28. O’Leary DP, Bhatt L, Woolley JF, et al. TLR-4 signalling accelerates colon cancer cell adhesion via NF-κB mediated transcriptional up-regulation of Nox-1. PLoS One. 2012;7(10):e44176. PMID: 23071493. PMCID: PMC3469572. https://doi.org/10.1371/journal.pone.0044176

29. Rahman AH, Taylor DK, Turka LA. The contribution of direct TLR signaling to T cell responses. Immunologic research. 2009;45(1):25–36. PMID: 19597998. PMCID: PMC4486050. https://doi.org/10.1007/s12026-009-8113-x


Review

For citations:


Kit O.I., Dzhenkova E.A., Mirzoyan E.A., Sagakyants A.B., Zlatnik E.Yu., Bondarenko E.S., Novikova I.A., Maslov A.A. Comparative analysis of some immunological parameters depending on the tumor location on the right and left sides of colon. Innovative Medicine of Kuban. 2022;(3):20-28. https://doi.org/10.35401/2541-9897-2022-25-3-20-28

Views: 324


ISSN 2541-9897 (Online)