Intracellular Levels of IL-10 and STAT3 in Patients with Chronic Lymphocytic Leukemia

Yıl 2023, Cilt: 13 Sayı: 1, 99 - 104, 28.03.2023

Ozden Ozcan , Yusuf Metin , Suzan Çınar , Gunnur Deniz , Melıh Aktan

https://doi.org/10.33808/clinexphealthsci.1056727

Öz

Objective: Chronic Lymphocytic Leukemia (CLL) is characterized by the accumulation of CD5+CD19+ B cells in the bone marrow and peripheral blood. Recent studies indicated that expression of IL-10, AID and mir-155 which are regulated by STAT3 are increased in CLL patients. CD5+CD19+ regulator B (Breg) cells secrete IL-10 and suppress the immune system. While the CLL cells show similar immunophenotypic properties to Breg cells, they are also thought to be functionally similar. In this study, STAT3 and IL-10 levels of CLL patients were investigated.
Methods: Peripheral blood samples obtained from patients (n:24) and healthy controls (n:14). Peripheral blood mononuclear cells were cultured for 48 hours in the presence and absence of CpG for IL-10 expression and cultured with and without PMA for STAT3 expression. IL-10 and STAT3 expression were analyzed with anti-CD5, anti-CD19, anti-CD38, anti-STAT3 and anti-IL-10 monoclonal antibodies by using flow cytometry.
Results: Compared to healthy subjects, increased IL-10+, IL-10+CD19+, STAT3+CD19+ were obtained in lymphocyte population of patients. Increased IL-10 was showed CD19+ B cells of CLL patients. Our results showed that IL-10 levels had no significant difference between CD5+CD19+ cells, whereas STAT3 levels were found lower in patient compared to healthy controls.
Conclusion: These results made us thought that the levels of IL-10 and STAT3 expression in CLL B cells is clearly different from normal B lymphocytes might have a role in the biology of CLL. It is believed that the presented data will contribute to the studies that scrutinize the similarity of CLL cells to Breg cells.

Anahtar Kelimeler

CLL, IL-10, STAT3, Breg, flow cytometry

Proje Numarası

Proje No: 55010.

Kaynakça

• Hallek M and Al-Sawaf O. Chronic lymphocytic leukemia: 2022 update on diagnostic and therapeutic procedures. Am J Hematol. 2021;96:1679–1705. DOI:10.1002/ajh.26367.
• Maliha K, Rabbia S, Philip AT. Approach to Richter transformation of chronic lymphocytic leukemia in the era of novel therapies. Ann Hematol. 2018; 97(1):1-15. DOI: 10.1007/s00277-017-3149-9.
• Catalán D. Mansilla MA, Ferrier A, Soto L, Oleinika K, Aguillon JC and Aravena O. Immunosuppressive mechanisms of regulatory B cells. Front Immunol. 2021;12:611795. DOI:10.3389/fimmu.2021.611795.
• Zhao Q and Jung LK. Frequency of CD19+ CD24hiCD38hi regulatory B cells is decreased in peripheral blood and synovial fluid of patients with juvenile idiopathic arthritis: a preliminary study. Pediatric Rheumatol Online J. 2018;16(1):44. DOI:10.1186/s12969-018-0262-9.
• Saulep-Easton D, Vincent FB, Quah PS, Wei A, Ting SB, Croce CM. The BAFF receptor TACI controls IL-10 production by regulatory B cells and CLL B-cells. Leukemia 2016; 30(1):163-172. DOI: 10.1038/leu.2015.174.
• Rutz S, Ouyang W. Regulation of interleukin-10 expression. Adv Exp Med Bio. 2016; 941:89-116. DOI: 10.1007/978-94-024-0921-5_5.
• Juliane L, Victor S, Johannes H, Christoph G. Jak-Stat signaling induced by interleukin-6 family cytokines in hepatocellular carcinoma. Cancers (Basel). 2019;11(11): 1704. DOI: 10.3390/cancers11111704.
• Liqun Y, Pengfei S, Gaichao, Zhao G, Xu J, Peng W, Zhang J, Zhang G,Wang X, Dong Z, Chen F and Cui H. Targeting cancer stem cell pathways for cancer therapy. Signal Transduct Target Ther. 2020; 5: 8. DOI:10.1038/s41392-020-0110-5.
• Wook J. Role of JAK/STAT3 Signaling in the regulation of metastasis, the transition of cancer stem cells, and chemoresistance of cancer by epithelial–mesenchymal transition. Cells 2020; 9(1): 217. DOI:10.3390/cells9010217.
• Chikuma S, Kanamori M, Mise-Omata S, Yoshimura A. Suppressors of cytokine signaling: potential immune checkpoint molecules for cancer immunotherapy. Cancer 2017; 108:574–580. DOI:10.1111/cas.13194.
• Daniel EJ, Rachel A. O’K, Jennifer RG. Targeting the IL-6/JAK/STAT3 signalling axis in cancer. Nat Rev Clin Oncol. 2018; 15(4): 234–248. DOI:10.1038/nrclinonc.2018.8.
• DiLillo DJ, Weinberg JB, Yoshizaki A, Horikawa M, Bryant JM, Iwata Y. Chronic lymphocytic leukemia and regulatory B cells share IL-10 competence and immunosuppressive function. Leukemia 2013; 27(1):170-182. DOI: 10.1038/leu.2012.165.
• Bewarder M, Stilgenbauer S, Thurner L, Kaddu-Mulindwa D. Current treatment options in CLL. Cancers (Basel). 2021; 13(10): 2468. DOI:10.3390/cancers13102468
• Alkan S. Kronik lenfositik lösemi (KLL): patogenezi ve biyolojisi. Türk Hematoloji Derneği. http://www.thd.org.tr/thdData/userfiles/file/kroniklenfositik.pdf7. 2006. (Turkish)
• Gupta R, Garg N. and Singh A. Anti-globulin test positivity indicates advanced disease in Indian CLL patients. Am J Blood Res. 2021; 11(2): 157–162.
• Liu Y. Liao S, Bennett S, Tang H, Song D, Wood D, Zhan X, and Xu J. STAT3 and its targeting inhibitors in osteosarcoma. Cell Prolif. 2021; 54(2): e12974. DOI: 10.1111/cpr.12974.
• Zhao J, FenQi Y, RongYu Y. STAT3: A key regulator in liver fibrosis. Annals of Hepatology 2021;100224. DOI:10.1016/j.aohep.2020.06.010.
• Antosz H, Wojciechowska K, Sajewicz J, Choroszynska D, Marzec-Kotarska B, Osiak M. IL-6, IL-10, c-Jun and STAT3 expression in B-CLL. Blood Cells Mol Dis. 2015; 54(3):258-265. DOI:10.1016/j.bcmd.2014.11.006.
• Gary-Gouy H, Harriague J, Bismuth G, Platze, C, Schmitt C, Dalloul AH. Human CD5 promotes B-cell survival through stimulation of autocrine IL-10 production. Blood 2002; 100:4537-4543. DOI:10.1182/blood-2002-05-1525.