The relationship between serum interleukin-1β and circulating CD16+ neutrophils for assessing progression-free time in advanced ovarian cancer

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Abstract

BACKGROUND: Ovarian cancer is the most aggressive gynecological tumor with high mortality. The ambivalent, both helper and suppressive effects of neutrophils on the cells of innate and adaptive immunity determines their important immunoregulatory role in the development of malignant tumors.

AIM: Evaluation of the effect of serum interleukin-1β and circulating neutrophils CD16+ on progression-free time in advanced ovarian cancer.

MATERIAL AND METHODS: In 42 primary patients with serous ovarian adenocarcinoma (median age 54 years) with ascites and 15 patients with benign ovarian tumors (median age 60 years) admitted for examination and treatment to the Regional Clinical Oncology Dispensary before receiving neoadjuvant antitumor treatment (2015–2020), the level of interleukin-1β in the blood serum was determined using enzyme immunoassay, and the number of CD16+ neutrophils was determined by fluorescence microscopy using monoclonal antibodies. Statistical processing was performed using Statistica 13 and Jamovi 2.4.14 programs. Progression-free time analysis of patients was performed using the Cox and Kaplan–Meier regression methods.

RESULTS: It was found that the number of circulating CD16+ neutrophils in advanced ovarian cancer with ascites was lower than in benign ovarian tumors [48.0; 95% confidence interval (CI) 46.59–48.12 versus 50.0; 95% CI 48.51–49.76; p=0.017]. At the same time, the level of interleukin-1β in the blood serum in advanced ovarian cancer with ascites was higher than in benign ovarian tumors [2.52 (95% CI 2.50–3.37) versus 1.26 (95% CI 0.97–1.55) (p=0.0001)]. In multivariate Cox analysis in patients with ascites (odds ratio 4.334; 95% CI 1.83–10.23; p=0.001), both the CD16+ neutrophil count (odds ratio 0.73; 95% CI 0.62–0.86; p=0.0001) and serum interleukin-1β levels (odds ratio 1.90; 95% CI 1.41–2.57; p=0.0001) had prognostic significance for assessing progression-free time.

CONCLUSION: The number of circulating CD16+ neutrophils and serum interleukin-1β levels simultaneously affect progression-free time in advanced ovarian cancer.

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About the authors

Tatyana V. Abakumova

Ulyanovsk State University

Author for correspondence.
Email: taty-abakumova@yandex.ru
ORCID iD: 0000-0001-7559-5246
SPIN-code: 8564-4253

Dr. Sci. (Biol.), Prof., Depart. of Physiology and Pathophysiology

Russian Federation, Ulyanovsk

Inna I. Antoneeva

Ulyanovsk State University; Regional Clinical Oncology Dispensary

Email: aii72@mail.ru
ORCID iD: 0000-0002-1525-2070
SPIN-code: 5305-5108

MD, Dr. Sci. (Med.), Prof., Depart. of Oncology and Radiation Diagnostics; Head of Depart., Gynecological Depart.

Russian Federation, Ulyanovsk; Ulyanovsk

Snezhanna O. Gening

BestDoctor LLC

Email: sgening@bk.ru
SPIN-code: 2496-2467

MD, Cand. Sci. (Med.), Oncologist

Russian Federation, Moscow

Elizaveta V. Burkhanova

Ulyanovsk State University

Email: burkhanova_e@inbox.ru
ORCID iD: 0009-0008-6955-9204
SPIN-code: 4883-1274

student

Russian Federation, Ulyanovsk

Tatyana P. Gening

Ulyanovsk State University

Email: Naum-53@yandex.ru
ORCID iD: 0000-0002-5117-1382
SPIN-code: 7285-8939

Dr. Sci. (Biol.), Prof., Head of Depart., Depart. of Physiology and Pathophysiology

Russian Federation, Ulyanovsk

References

  1. Ravindran F, Choudhary B. Ovarian cancer: Molecular classification and targeted therapy. In: Ho G, Webber K, editors. Ovarian cancer — updates in tumor biology and therapeutics. London: IntechOpen; 2021. р. 1–21. doi: 10.5772/intechopen.95967
  2. Ueki A, Hirasawa A. Molecular features and clinical management of hereditary gynecological cancers. Int J Mol Sci. 2020;21(24):9504. doi: 10.3390/ijms21249504
  3. Coleridge SL, Bryant A, Kehoe S, Morrison J. Neoadjuvant chemotherapy before surgery versus surgery followed by chemotherapy for initial treatment in advanced ovarian epithelial cancer. Cochrane Database Syst Rev. 2021;7(7):CD005343. doi: 10.1002/14651858.CD005343
  4. Súarez-Zaizar A, Cárdenas-Cárdenas E, Barajas-Castro YA, Cortés-Esteban P. Controversies on the treatment of ovarian cancer with dose-dense chemotherapy. Chin Clin Oncol. 2020;9(4):53. doi: 10.21037/cco-2019-oc-12
  5. Dosch AR, Singh S, Dai X, Mehra S, Silva IC, Bianchi A, Srinivasan S, Gao Z, Ban Y, Chen X, Banerjee S, Nagathihalli NS, Datta J, Merchant NB. Targeting tumor-stromal IL6/STAT3 signaling through IL1 receptor inhibition in pancreatic cancer. Mol Cancer Ther. 2021;20(11):2280–2290. doi: 10.1158/1535-7163.MCT-21-0083
  6. Baker KJ, Houston A, Brint E. IL-1 family members in cancer; Two sides to every story. Front Immunol. 2019;10:1197. doi: 10.3389/fimmu.2019.01197
  7. Kuan EL, Ziegler SF. A tumor-myeloid cell axis, mediated via the cytokines IL-1alpha and TSLP, promotes the progression of breast cancer. Nat Immunol. 2018;19(4):366–374. doi: 10.1038/s41590-018-0066-6
  8. Liu S, Lee JS, Jie C, Park MH, Iwakura Y, Patel Y, Soni M, Reisman D, Chen H. HER2 overexpression triggers an IL1α proinflammatory circuit to drive tumorigenesis and promote chemotherapy resistance. Cancer Res. 2018;78(8):2040–2051. doi: 10.1158/0008-5472.CAN-17-2761
  9. Dolgushin II. Neutrophil granulocytes: new faces of old acquaintances. Byulleten' sibirskoi meditsiny. 2019;18(1):30–37. (In Russ.) doi: 10.20538/1682-0363-2019-1-30-37
  10. Chen S, Zhang Q, Lu L, Xu C, Li J, Zha J, Ma F, Luo HR, Hsu AY. Heterogeneity of neutrophils in cancer: One size does not fit all. Cancer Biol Med. 2022;19(12):1629–1648. doi: 10.20892/j.issn.2095-3941.2022.0426
  11. Treffers LW, van Houdt M, Bruggeman CW, Heineke MH, Zhao XW, van der Heijden J, Nagelkerke SQ, Verkuijlen PJJH, Geissler J, Lissenberg-Thunnissen S, Valerius T, Peipp M, Franke K, van Bruggen R, Kuijpers TW, van Egmond M, Vidarsson G, Matlung HL, van den Berg TK. FcgammaRIIIb restricts antibody-dependent destruction of cancer cells by human neutrophils. Front Immunol. 2019;9:3124. doi: 10.3389/fimmu.2018.03124
  12. Gasparoto TH, Dalboni TM, Amôr NG, Abe AE, Perri G, Lara VS, Vieira NA, Gasparoto CT, Campanelli AP. Fcγ receptors on aging neutrophils. J Appl Oral Sci. 2021;29:e20200770. doi: 10.1590/1678-7757-2020-0770
  13. Alemán OR, Rosales C. Human neutrophil Fc gamma receptors: Different buttons for different responses. J Leukoc Biol. 2023;114(6):571–584. doi: 10.1093/jleuko/qiad080
  14. Grieshaber-Bouyer R, Nigrovic PA. Neutrophil heterogeneity as therapeutic opportunity in immune-mediated disease. Front Immunol. 2019;10:346. doi: 10.3389/fimmu.2019.00346
  15. Vorobjeva N, Dagil Y, Pashenkov M, Pinegin B, Chernyak B. Protein kinase C isoforms mediate the formation of neutrophil extracellular traps. Int Immunopharmacol. 2023;114:109448. doi: 10.1016/j.intimp.2022.109448
  16. Chang Y, Syahirah R, Wang X, Jin G, Torregrosa-Allen S, Elzey BD, Hummel SN, Wang T, Li C, Lian X, Deng Q, Broxmeyer HE, Bao X. Engineering chimeric antigen receptor neutrophils from human pluripotent stem cells for targeted cancer immunotherapy. Cell Rep. 2022;40(3):111128. doi: 10.1016/j.celrep.2022.111128
  17. Rakic A, Beaudry P, Mahoney DJ. The complex interplay between neutrophils and cancer. Cell Tissue Res. 2018;371(3):517–529. doi: 10.1007/s00441-017-2777-7
  18. Tu S, Bhagat G, Cui G, Takaishi S, Kurt-Jones EA, Rickman B, Betz KS, Penz-Oesterreicher M, Bjorkdahl O, Fox JG, Wang TC. Overexpression of interleukin-1beta induces gastric inflammation and cancer and mobilizes myeloid-derived suppressor cells in mice. Cancer Cell. 2008;14(5):408–419. doi: 10.1016/j.ccr.2008.10.011
  19. Masucci MT, Minopoli M, Carriero MV. Tumor associated neutrophils. Their role in tumorigenesis, metastasis, prognosis and therapy. Front Oncol. 2019;9:1146. doi: 10.3389/fonc.2019.01146
  20. Costa AC, Santos JMO, Gil da Costa RM, Medeiros R. Impact of immune cells on the hallmarks of cancer: A literature review. Crit Rev Oncol Hematol. 2021;168:103541. doi: 10.1016/j.critrevonc.2021.103541
  21. Takahashi R, Macchini M, Sunagawa M, Jiang Z, Tanaka T, Valenti G, Renz BW, White RA, Hayakawa Y, Westphalen CB, Tailor Y, Iuga AC, Gonda TA, Genkinger J, Olive KP, Wang TC. Interleukin-1β-induced pancreatitis promotes pancreatic ductal adenocarcinoma via B lymphocyte-mediated immune suppression. Gut. 2021;70(2):330–341. doi: 10.1136/gutjnl-2019-319912
  22. Nishida J, Momoi Y, Miyakuni K, Tamura Y, Takahashi K, Koinuma D, Miyazono K, Ehata S. Epigenetic remodelling shapes inflammatory renal cancer and neutrophil-dependent metastasis. Nat Cell Biol. 2020;22(4):465–475. doi: 10.1038/s41556-020-0491-2
  23. Rogers T, DeBerardinis RJ. Metabolic plasticity of neutrophils: Relevance to pathogen responses and cancer. Trends Cancer. 2021;7(8):700–713. doi: 10.1016/j.trecan.2021.04.007
  24. Coffelt SB, Wellenstein MD, de Visser KE. Neutrophils in cancer: Neutral no more. Nat Rev Cancer. 2016;16:431–446. doi: 10.1038/nrc.2016.52
  25. Shaul ME, Fridlender ZG. Neutrophils as active regulators of the immune system in the tumor microenvironment. J Leukoc Biol. 2017;102:343–349. doi: 10.1189/jlb.5MR1216-508R
  26. Guthrie GJ, Charles KA, Roxburgh CS, Horgan PG, McMillan DC, Clarke SJ. The systemic inflammation-based neutrophil-lymphocyte ratio: Experience in patients with cancer. Crit Rev Oncol Hematol. 2013;88:218–230. doi: 10.1016/j.critrevonc.2013.03.010
  27. Zhou Y, Wei Q, Fan J, Cheng S, Ding W, Hua Z. Prognostic role of the neutrophil-to-lymphocyte ratio in pancreatic cancer: A meta-analysis containing 8252 patients. Clin Chim Acta. 2018;479:181–189. doi: 10.1016/j.cca.2018.01.024
  28. Verschoor CP, Loukov D, Naidoo A, Puchta A, Johnstone J, Millar J, Lelic A, Novakowski KE, Dorrington MG, Loeb M, Bramson JL, Bowdish DM. Circulating TNF and mitochondrial DNA are major determinants of neutrophil phenotype in the advanced-age, frail elderly. Mol Immunol. 2015;65(1):148–156. doi: 10.1016/j.molimm.2015.01.015
  29. Fossati G, Moots RJ, Bucknall RC, Edwards SW. Differential role of neutrophil Fcgamma receptor IIIB (CD16) in phagocytosis, bacterial killing, and responses to immune complexes. Arthritis Rheum. 2002;46(5):1351–1361. doi: 10.1002/art.10230

Supplementary files

Supplementary Files
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1. JATS XML
2. Fig. 1. Progression-free time curve in patients with advanced ovarian cancer depending on the level of interleukin-1β (IL-1β) in the blood

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3. Fig. 2. Progression-free time curve in patients with advanced ovarian cancer depending on the number of circulating CD16+ neutrophils

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4. Fig. 3. ROC curve characterizing the dependence of the relapse probability on the levels of interleukin-1β and CD16+ neutrophils in the blood (AUC=0.957)

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