Possibility of modification of peripheral blood neutrophils functional activity during chemoradiotherapy in patients with anorectal cancer

Background. Ionizing radiation is an effective antitumor therapy, but it has a serious negative effect on the immune system requiring the use of radiation reaction prevention and reduction methods. Neutrophils are a sensitive element of the immune system both in interaction with tumor tissue and in response to radiation injury.

Aim. To evaluate functional activity of peripheral blood neutrophils by chemiluminescent analysis in patients with anorectal cancer after radiotherapy.

Materials and methods. The study included 80 patients with anorectal cancer. Patients received chemo- and radio-therapy with 3D conformal radiotherapy and radiation therapy under visual control, followed by the use of radioprotector and without it. Neutrophil activity determined by chemiluminescent analysis.

Results. In patients with anorectal cancer found maximum spontaneous and induced chemiluminescence acceleration. The chemiluminescence activation index with luminol is lower in patients with anorectal cancer, and with lucigenin shows no differences with the control group. The low luminol chemiluminescence maximum intensity, as well as the decrease in the synthesis of reactive secondary oxygen species in enzymatic systems, is likely regulatory intracellular limitations consequence. After treatment, patients with radioprotector showed a decrease in the number of parameters with statistically significant differences with the control group. Undesirable phenomena associated with sodium deoxyribonucleate therapy not detected in anorectal cancer patients during radiotherapy and subsequent observation period.

Conclusion. During treatment, differences in chemiluminescence parameters suggest that ionizing radiation affects them in patients with anorectal cancer receiving standard chemoradiotherapy. Use of chemoradiotherapy with a radioprotector leads to indirect restoration of cellular functional activity. This is confirmed by luminol-dependent chemiluminescence faster reaching its maximum and a decrease in the number of significant differences from the control group after the start of the drug treatment.

1. Kay A.B. Paul Ehrlich and the early history of granulocytes. Microbiol Spectr 2016;4(4). DOI: 10.1128/microbiolspec.MCHD-0032-2016

2. Ambrose C.T. The Osler slide, a demonstration of phagocytosis from 1876 Reports of phagocytosis before Metchnikoff's 1880 paper. Cell Immunol 2006;240(1):1-4. DOI: 10.1016/j.cellimm.2006.05.008

3. https://www.nobelprize.org/prizes/medicine/1908/summary/.

4. Mackey J.B.G., Coffelt S.B., Carlin L.M. Neutrophil maturity in cancer. Front Immunol 2019;10:1912. DOI: 10.3389/fimmu.2019.01912

5. Giese M.A., Hind L.E., Huttenlocher A. Neutrophil plasticity in the tumor microenvironment. Blood 2019;133(20):2159-67. DOI: 10.1182/blood-2018-11-844548

6. Lecot P., Sarabi M., Pereira Abrantes M. et al. Neutrophil heterogeneity in cancer: from biology to therapies. Front Immunol 2019;10:2155. DOI: 10.3389/fimmu.2019.02155

7. Coffelt S.B., Wellenstein M.D., de Visser K.E. Neutrophils in cancer: neutral no more. Nat Rev Cancer 2016;16(7):431-46. DOI: 10.1038/nrc.2016.52

8. Baldueva I.A., Zozulya A.Yu., Novikov S.N. Stereotaxic radiotherapy in the light of systemic immunological effects. Zlokachestvenniye opukholi = Malignant Tumors 2019;9(3s1):23—5. (In Russ.). DOI: 10.18027/2224-5057-2019-9-3s1-23-25

9. Schaue D., McBride W.H. Opportunities and challenges of radiotherapy for treating cancer. Nat Rev Clin Oncol 2015;12(9):527-40. DOI: 10.1038/nrclinonc.2015.120

10. Sermeus A., Leonard W., Engels B., De Ridder M. Advances in radiotherapy and targeted therapies for rectal cancer. World J Gastroenterol 2014;20(1):1-5. DOI: 10.3748/wjg.v20.i1.1

11. De Sole P. Polymorphonuclear chemiluminescence: some clinical applications. J Biolumin Chemilumin 1989;4(1):251-62. DOI: 10.1002/bio.1170040136