CORRELATIONS BETWEEN PERIPHERAL BLOOD INFLAMMATORY MARKERS AND INTERLEUKIN-21 IN PATIENTS WITH HEMATOLOGIC MALIGNANCIES

CORRELATIONS BETWEEN PERIPHERAL BLOOD INFLAMMATORY MARKERS AND INTERLEUKIN-21 IN PATIENTS WITH HEMATOLOGIC MALIGNANCIES

Authors

  • NINO NANAVA
  • GIORGI GIORGOBIANI
  • NINO KIKODZE
  • SOPHIO METREVELI
  • TINATIN CHIKOVANI
  • NONA JANIKASHVILI

DOI:

https://doi.org/10.52340/jecm.2022.03.16

Keywords:

inflammatory markers, interleukin-21, hematologic malignancies

Abstract

Inflammation that occurs in the tumor microenvironment and in the systemic circulation correlates with disease progression and prognosis in a number of tumors. One way to assess the systemic immune response is to determine the cells/their ratio associated with inflammation, which can easily be measured with complete blood count. IL-21 has a variety of regulatory effects on both normal and tumor cells, leading to their proliferation, differentiation, and apoptosis.The aim of our study was to determine the level of IL-21 in patients with lymphoma-leukemia and to correlate it with the biomarkers of systemic inflammation involved in carcinogenesis - NLR, PLR, PMR, HLR, SII, dNLR.The study included patients with hematologic tumors who underwent splenectomy for therapeutic indications. The control group consisted of patients who also underwent splenectomy but not due to malignant tumor or autoimmune disease.According to our study analysis interleukin-21 levels did not differ significantly between the study and control groups. Serum levels of interleukin-21 in patients with malignant hematologic tumors are negatively correlated with dNLR.

Downloads

Download data is not yet available.

References

G. J. K. Guthrie, C. S. D. Roxburgh, O. M. Farhan-Alanie, P. G. Horgan, and D. C. McMillan, “Comparison of the prognostic value of longitudinal measurements of systemic inflammation in patients undergoing curative resection of colorectal cancer,” Br. J. Cancer 2013 1091, vol. 109, no. 1, pp. 24–28, Jun. 2013, doi: 10.1038/bjc.2013.330.

J. Candido and T. Hagemann, “Cancer-Related Inflammation,” J. Clin. Immunol. 2012 331, vol. 33, no. 1, pp. 79–84, Dec. 2012, doi: 10.1007/S10875-012-9847-0.

C. Servais and N. Erez, “From sentinel cells to inflammatory culprits: cancer-associated fibroblasts in tumour-related inflammation,” J. Pathol., vol. 229, no. 2, pp. 198–207, Jan. 2013, doi: 10.1002/PATH.4103.

L. M. Coussens and Z. Werb, “Inflammation and cancer,” Nat. 2002 4206917, vol. 420, no. 6917, pp. 860–867, Dec. 2002, doi: 10.1038/nature01322.

A. Stoppacciaro et al., “Regression of an established tumor genetically modified to release granulocyte colony-stimulating factor requires granulocyte-T cell cooperation and T cell-produced interferon gamma.,” J. Exp. Med., vol. 178, no. 1, pp. 151–161, Jul. 1993, doi: 10.1084/JEM.178.1.151.

M. D. Fesinmeyer, M. A. Austin, C. I. Li, A. J. De Roos, and D. J. Bowen, “Differences in Survival by Histologic Type of Pancreatic Cancer,” Cancer Epidemiol. Biomarkers Prev., vol. 14, no. 7, pp. 1766–1773, Jul. 2005, doi: 10.1158/1055-9965.EPI-05-0120.

M. Schmidt et al., “The Humoral Immune System Has a Key Prognostic Impact in Node-Negative Breast Cancer,” Cancer Res., vol. 68, no. 13, pp. 5405–5413, Jul. 2008, doi: 10.1158/0008-5472.CAN-07-5206.

J. M. Matos et al., “Pancreatic Acinar Cell Carcinoma: A Multi-institutional Study,” J. Gastrointest. Surg. 2009 138, vol. 13, no. 8, pp. 1495–1502, Jun. 2009, doi: 10.1007/S11605-009-0938-Z.

J. L. Sylman et al., “The predictive value of inflammation-related peripheral blood measurements in cancer staging and prognosis,” Front. Oncol., vol. 8, no. MAR, p. 78, Mar. 2018, doi: 10.3389/FONC.2018.00078/BIBTEX.

N. Nanava, M. Betaneli, G. Giorgobiani, T. Chikovani, and N. Janikashvili, “COMPLETE BLOOD COUNT DERIVED INFLAMMATORY BIOMARKERS IN PATIENTS WITH HEMATOLOGIC MALIGNANCIES,” Georgian Med. News, no. 302, pp. 39–44, May 2020.

S. Bhatt, K. A. Sarosiek, and I. S. Lossos, “Interleukin 21 – its potential role in the therapy of B-cell lymphomas,” Leuk. Lymphoma, vol. 58, no. 1, pp. 17–29, 2017, doi: 10.1080/10428194.2016.1201568.

E. K. Curran, J. Godfrey, and J. Kline, “Mechanisms of Immune Tolerance in Leukemia and Lymphoma,” Trends Immunol., vol. 38, no. 7, pp. 513–525, Jul. 2017, doi: 10.1016/J.IT.2017.04.004.

A. L. Wurster et al., “Interleukin 21 is a T helper (Th) cell 2 cytokine that specifically inhibits the differentiation of naive Th cells into interferon γ-producing Th1 cells,” J. Exp. Med., vol. 196, no. 7, pp. 969–977, 2002, doi: 10.1084/jem.20020620.

A. Suto et al., “Interleukin 21 prevents antigen-induced IgE production by inhibiting germ line Cε transcription of IL-4–stimulated B cells,” Blood, vol. 100, no. 13, pp. 4565–4573, Dec. 2002, doi: 10.1182/BLOOD-2002-04-1115.

M. Strengell, T. Sareneva, D. Foster, I. Julkunen, and S. Matikainen, “IL-21 Up-Regulates the Expression of Genes Associated with Innate Immunity and Th1 Response,” J. Immunol., vol. 169, no. 7, pp. 3600–3605, Oct. 2002, doi: 10.4049/JIMMUNOL.169.7.3600.

R. Zeng et al., “Synergy of IL-21 and IL-15 in regulating CD8+ T cell expansion and function,” J. Exp. Med., vol. 201, no. 1, pp. 139–148, Jan. 2005, doi: 10.1084/JEM.20041057.

Y. Li, M. Bleakley, and C. Yee, “IL-21 Influences the Frequency, Phenotype, and Affinity of the Antigen-Specific CD8 T Cell Response,” J. Immunol., vol. 175, no. 4, pp. 2261–2269, Aug. 2005, doi: 10.4049/JIMMUNOL.175.4.2261.

I. Peluso et al., “IL-21 counteracts the regulatory T cell-mediated suppression of human CD4+ T lymphocytes,” J. Immunol., vol. 178, no. 2, pp. 732–739, Jan. 2007, doi: 10.4049/JIMMUNOL.178.2.732.

H. He et al., “Combined IL-21 and low-dose IL-2 therapy induces anti-tumor immunity and long-term curative effects in a murine melanoma tumor model,” J. Transl. Med., vol. 4, no. 1, pp. 1–16, Jun. 2006, doi: 10.1186/1479-5876-4-24/FIGURES/7.

D. De Totero et al., “The opposite effects of IL-15 and IL-21 on CLL B cells correlate with differential activation of the JAK/STAT and ERK1/2 pathways,” Blood, vol. 111, no. 2, pp. 517–524, Jan. 2008, doi: 10.1182/BLOOD-2007-04-087882.

L. Wu, B. Ehlin-Henriksson, H. Zhu, I. Ernberg, and G. Klein, “EBV counteracts IL-21-induced apoptosis in an EBV-positive diffuse large B-cell lymphoma cell line,” Int. J. Cancer, vol. 133, no. 3, pp. 766–770, Aug. 2013, doi: 10.1002/IJC.28067.

P. Gelebart, Z. Zak, M. Anand, J. Dien-Bard, H. M. Amin, and R. Lai, “Interleukin-21 effectively induces apoptosis in mantle cell lymphoma through a STAT1-dependent mechanism,” Leuk. 2009 2310, vol. 23, no. 10, pp. 1836–1846, Jun. 2009, doi: 10.1038/leu.2009.100.

D. de Totero et al., “Heterogeneous expression and function of IL-21R and susceptibility to IL-21-mediated apoptosis in follicular lymphoma cells,” Exp. Hematol., vol. 38, no. 5, pp. 373–383, May 2010, doi: 10.1016/J.EXPHEM.2010.02.008.

B. Wood et al., “Abundant expression of interleukin-21 receptor in follicular lymphoma cells is associated with more aggressive disease,” Leuk. Lymphoma, vol. 54, no. 6, pp. 1212–1220, Jun. 2013, doi: 10.3109/10428194.2012.742522.

B. E. Wahlin et al., “A unifying microenvironment model in follicular lymphoma: outcome is predicted by programmed death-1--positive, regulatory, cytotoxic, and helper T cells and macrophages,” Clin. Cancer Res., vol. 16, no. 2, pp. 637–650, Jan. 2010, doi: 10.1158/1078-0432.CCR-09-2487.

J. D. Bard et al., “IL-21 contributes to JAK3/STAT3 activation and promotes cell growth in ALK-positive anaplastic large cell lymphoma,” Am. J. Pathol., vol. 175, no. 2, pp. 825–834, 2009, doi: 10.2353/AJPATH.2009.080982.

E. Ménoret et al., “IL-21 Stimulates Human Myeloma Cell Growth through an Autocrine IGF-1 Loop,” J. Immunol., vol. 181, no. 10, pp. 6837–6842, Nov. 2008, doi: 10.4049/JIMMUNOL.181.10.6837.

F. A. Scheeren et al., “IL-21 is expressed in Hodgkin lymphoma and activates STAT5: evidence that activated STAT5 is required for Hodgkin lymphomagenesis,” Blood, vol. 111, no. 9, pp. 4706–4715, May 2008, doi: 10.1182/BLOOD-2007-08-105643.

M. R. Galdiero, E. Bonavita, I. Barajon, C. Garlanda, A. Mantovani, and S. Jaillon, “Tumor associated macrophages and neutrophils in cancer,” Immunobiology, vol. 218, no. 11, pp. 1402–1410, Nov. 2013, doi: 10.1016/J.IMBIO.2013.06.003.

Y. H. Kusumanto, W. A. Dam, G. A. P. Hospers, C. Meijer, and N. H. Mulder, “Platelets and Granulocytes, in Particular the Neutrophils, Form Important Compartments for Circulating Vascular Endothelial Growth Factor,” Angiogenes. 2003 64, vol. 6, no. 4, pp. 283–287, 2003, doi: 10.1023/B:AGEN.0000029415.62384.BA.

L. Benevides et al., “IL17 promotes mammary tumor progression by changing the behavior of tumor cells and eliciting tumorigenic neutrophils recruitment,” Cancer Res., vol. 75, no. 18, pp. 3788–3799, Sep. 2015, doi: 10.1158/0008-5472.CAN-15-0054/651853/AM/IL-17-PROMOTES-MAMMARY-TUMOR-PROGRESSION-BY.

C. A. Dumitru, S. Lang, and S. Brandau, “Modulation of neutrophil granulocytes in the tumor microenvironment: Mechanisms and consequences for tumor progression,” Semin. Cancer Biol., vol. 23, no. 3, pp. 141–148, Jun. 2013, doi: 10.1016/J.SEMCANCER.2013.02.005.

G. Bellone et al., “Tumor-Associated Transforming Growth Factor-β and Interleukin-10 Contribute to a Systemic Th2 Immune Phenotype in Pancreatic Carcinoma Patients,” Am. J. Pathol., vol. 155, no. 2, pp. 537–547, Aug. 1999, doi: 10.1016/S0002-9440(10)65149-8.

M. J. Proctor, D. C. McMillan, D. S. Morrison, C. D. Fletcher, P. G. Horgan, and S. J. Clarke, “A derived neutrophil to lymphocyte ratio predicts survival in patients with cancer,” Br. J. Cancer, vol. 107, no. 4, p. 695, Aug. 2012, doi: 10.1038/BJC.2012.292.

D. Y. Kim et al., “Clinical impacts of inflammatory markers and clinical factors in patients with relapsed or refractory diffuse large B-cell lymphoma,” Blood Res., vol. 54, no. 4, p. 244, 2019, doi: 10.5045/BR.2019.54.4.244.

H. Hong, X. Fang, H. Huang, Z. Wang, T. Lin, and H. Yao, “The derived neutrophil-to-lymphocyte ratio is an independent prognostic factor in patients with angioimmunoblastic T-cell lymphoma,” Br. J. Haematol., vol. 189, no. 5, pp. 908–912, Jun. 2020, doi: 10.1111/BJH.16447.

B. Uz, “The Prognostic Value of the Derived Neutrophil-to-Lymphocyte Ratio in Transplantation-Ineligible Patients with Multiple Myeloma,” Acta Haematol., vol. 140, no. 3, pp. 157–158, Oct. 2018, doi: 10.1159/000491988.

Y. Wang et al., “Preoperative neutrophil-to-lymphocyte ratio predicts response to first-line platinum-based chemotherapy and prognosis in serous ovarian cancer,” Cancer Chemother. Pharmacol. 2014 752, vol. 75, no. 2, pp. 255–262, Nov. 2014, doi: 10.1007/S00280-014-2622-6.

B. Azab et al., “Usefulness of the Neutrophil-to-Lymphocyte Ratio in Predicting Short- and Long-Term Mortality in Breast Cancer Patients,” Ann. Surg. Oncol. 2011 191, vol. 19, no. 1, pp. 217–224, Jun. 2011, doi: 10.1245/S10434-011-1814-0.

L. Stevens et al., “Prognostic significance of pre-operative C-reactive protein and the neutrophil–lymphocyte ratio in resectable pancreatic cancer: a systematic review,” HPB, vol. 17, no. 4, pp. 285–291, Apr. 2015, doi: 10.1111/HPB.12355.

Downloads

Published

2022-04-11

How to Cite

NINO NANAVA, GIORGI GIORGOBIANI, NINO KIKODZE, SOPHIO METREVELI, TINATIN CHIKOVANI, & NONA JANIKASHVILI. (2022). CORRELATIONS BETWEEN PERIPHERAL BLOOD INFLAMMATORY MARKERS AND INTERLEUKIN-21 IN PATIENTS WITH HEMATOLOGIC MALIGNANCIES . Experimental and Clinical Medicine Georgia, (3). https://doi.org/10.52340/jecm.2022.03.16

Issue

Section

Articles

Most read articles by the same author(s)

Similar Articles

<< < 1 2 3 4 5 > >> 

You may also start an advanced similarity search for this article.

Loading...