Effect of dendritic cell vaccine on blood redox status in patients with cervical cancer

Purpose of the study. The purpose of the study was to evaluate the dynamics of parameters of malondialdehyde (MDA), reduced glutathione and antioxidant enzyme activity in patients with advanced cervical cancer (CC) receiving anticancer treatment with dendritic cell vaccine (DCV).

Patients and methods. Levels of malondialdehyde (MDA), reduced glutathione and antioxidant enzyme activity were studied in 27 patients aged 27–65 years with advanced primary and recurrent CC receiving chemotherapy (CT) with DCV or DCV as monotherapy at a dose of 10 million cells intradermally once a week. The same indices were studied in 20 healthy women from the comparison group.

Results. The majority of patients showed the initial increase of MDA: in blood plasma by an average of 66.7 %, in red blood cells – statistically insignificant. After CT, MDA levels were elevated respectively in primary and recurrent patients in erythrocytes by 85.6 % and 96.4 % compared to donors, and by 53.9 % and 33.7 % compared to the initial values; the levels in plasma were elevated by 79.8 % and 57.1 % compared to donors. After 5–7 DCVs in combination with CT, MDA levels in erythrocytes and in blood plasma were similar to the donor values. MDA in erythrocytes of patients receiving DCV without CT decreased by 36 % compared to initial values. Oxidase activity of ceruloplasmin, initially increased by 34.2–57.1 %, normalized after DCV. Superoxide dismutase activity decreased by 16.7–27.3 % after 4–6 DCVs and normalized after 7 DCVs. Catalase activity, initially reduced by more than 40 %, remained 20–38 % lower than the norm at all stages of DCV. In this setting, hydrogen peroxide was probably inactivated by glutathione peroxidase whose activity was increased at all stages of treatment and decreased only when MDA was normalized after 7 DCVs.

Conclusion. Administration of 5–7 DCVs in combination with CT or as monotherapy to patients with advanced CC normalizes parameters of free radical oxidation and antioxidant system of the blood.

1. Odintsova IN, Pisareva LF, Pikalova LV, Kudyakov LA. Epidemiological aspects of gynecologic cancer in Tomsk region. Siberian Journal of Oncology. 2017;16(5):48–54. (In Russ.). https://doi.org/10.21294/1814‑4861‑2017‑16‑5‑48‑54

2. Chernyshova AL, Kolomiets LA, Chernov VI. Radical trachelectomy for cervical cancer. Novosibirsk, 2020 (In Russ.).

3. Malignant neoplasms in Russia in 2021 (morbidity and mortality). Edited by Kaprin AD, Starinsky VV, Shakhzadova AO. Мoscow: P. Hertsen Moscow Oncology Research Institute – Branch of the National Medical Radiology Research Centre of the Ministry of Health of the Russian Federation, 2022, 239 p. (In Russ.). Available at: https://oncology‑association.ru/wp-content/uploads/2022/05/sostoyanie-onkologicheskoj-pomoshhi-naseleniyu-rossii-v-2021-godu.pdf Accessed: 30.01.2023.

4. Vodolazhskiy DI, Menshenina AP, Dvadnenko KV, Novikova IA, Zlatnik EY, Bakhtin AV, et al. Experience of dendritic cell vaccine design for cervical cancer treatment. Fundamental Research. 2015;1‑4:716–720. (In Russ.). URL: http://www.fundamental‑research.ru/ru/article/view?id=37407

5. Saha A, Chatterjee SK, Foon KA, Primus FJ, Sreedharan S, Mohanty K, Bhattacharya‑Chatterjee M. Dendritic cells pulsed with an anti‑idiotype antibody mimicking carcinoembryonic antigen (CEA) can reverse immunological tolerance to CEA and induce antitumor immunity in CEA transgenic mice. Cancer Res. 2004 Jul 15;64(14):4995–5003. https://doi.org/10.1158/0008‑5472.can‑04‑0626

6. Sies H, Berndt C, Jones DP. Oxidative Stress. Annu Rev Biochem. 2017 Jun 20;86:715‑748. https://doi.org/10.1146/annurev‑biochem‑061516‑045037

7. Andrisic L, Dudzik D, Barbas C, Milkovic L, Grune T, Zarkovic N. Short overview on metabolomics approach to study pathophysiology of oxidative stress in cancer. Redox Biol. 2018 Apr;14:47–58. https://doi.org/10.1016/j.redox.2017.08.009

8. Prasad S, Gupta SC, Tyagi AK. Reactive oxygen species (ROS) and cancer: Role of antioxidative nutraceuticals. Cancer Lett. 2017 Feb 28;387:95–105. https://doi.org/10.1016/j.canlet.2016.03.042

9. Dawane JS, Pandit VA. Understanding redox homeostasis and its role in cancer. J Clin Diagn Res. 2012 Dec;6(10):1796–1802. https://doi.org/10.7860/jcdr/2012/4947.2654

10. Kashyap D, Tuli HS, Sak K, Garg VK, Goel N, Punia S, Chaudhary A. Role of Reactive Oxygen Species in Cancer Progression. Current Pharmacology Reports. 2019;5:79–86. https://doi.org/10.1007/s40495‑019‑00171‑y

11. Corso CR, Acco A. Glutathione system in animal model of solid tumors: From regulation to therapeutic target. Crit Rev Oncol Hematol. 2018 Aug;128:43–57. https://doi.org/10.1016/j.critrevonc.2018.05.014

12. Menshchikova EB, Zenkov NK, Lankin VZ, Bondar IA, Trufakin VA. Oxidative stress. Pathological conditions and diseases. Novosibirsk: Siberian University Publ.; 2017. (In Russ.).

13. Goroshinskaya I, Popova N, Menshenina A, Nemashkalova L, Shikhlyarova A, Frantsiyants E, et al. Free radical processes in the blood of patients with cervical cancer receiving various postoperative treatment modalities. International Journal of Gynecologic Cancer. 2019;29:A218–A219.

14. Goroshinskaya IA, Surikova EI, Frantsiyants EM, Nemashkalova LA, Kachesova PS, Medvedeva DE, Maslov AA. Glutathione‑dependent system in the blood of gastric cancer patients with various tumor histotypes and prevalence of the disease. Research and Practical Medicine Journal. https://doi.org/10.17709/2410‑1893‑2021‑8‑4‑1

15. Arutynyan AV, Dubinina EE, Zybina NN. Methods for assessing free radical oxidation and the antioxidant system of the body. Guidelines. St. Petersburg: “Foliant” Publ.; 2000. (In Russ.).

16. Methods of clinical laboratory research. Edited by Kamyshnikov VS. Moscow: “MEDpress‑inform” Publ.; 2013. (In Russ.).

17. Korn EL, Troendle JF, McShane LM, Simon R. Controlling the number of false discoveries: application to high‑dimensional genomic data. Journal of Statistical Planning and Inference. 2004;124(2): 379–398. https://doi.org/10.1016/s0378‑3758(03)00211‑8

18. Gerasimenko MN, Zukov RA, Titova NM, Dykhno YuA, Modestov AA, Popov DV. Antioxidant system and markers of oxidative stress in renal cell cancer. Siberian Journal of Oncology. 2012;5(53):39–43. (In Russ.).

19. Goroshinskaya IA, Frantsiyants EM, Aleynov VI, Nemashkalova LA, Cheryarina ND, Kit OI. Parameters of oxidative metabolism in the blood of patients with pancreatic tumors of various histotype. Modern Problems of Science and Education. 2020;2:89. (In Russ.). https://doi.org/10.17513/spno.29548

20. Goroshinskaya IA, Surikova EI, Shalashnaya EV, Nerodo GA, Maximova NA, Menshenina AP, et al. State of free radical processes in ovarian cancer with different prevalence and course of the disease. Bulletin Of Higher Education Institutes. North Caucasus Region. Natural Sciences. 2017;4‑2 (196‑2):10–19. (In Russ.).