Evaluation The Role of CD33+ CD11b+ myeloid-derived Suppressor Cells in Patients With AML

Hamad, Hala Mahdi; Shabeeb, Zeyad Ahmed; Awad, Muthanna M.

doi:10.37652/juaps.2022.174817

Document Type : Research Paper

Authors

¹ Department of Biology , Collage of Science , University Of Anbar , Anbar , Iraq

² National center of hematology , University Of Mustansiriyah, Baghdad , Iraq

³ Department of Biology , College of Education for Pure Sciences , University Of Anbar , Anbar , Iraq

https://doi.org/10.37652/juaps.2022.174817

Abstract

Acute myeloid leukemia is a genetically heterogeneous clonal disease defined by the accumulation of immature cells in bone marrow and blood. The aim of this study is to evaluate the CD33, CD11b, and HLA-DR expression in Iraqi AML patients and its role in evasion of malignant cells from the immune system. This study was conducted on 60 patients with AML and 20 healthy individuals as a control group to evaluate the expression of CD33 and CD11b using flow-cytometry in peripheral blood, and evaluate Interferons-γ (IFN-γ) and Transforming Growth Factor-β1 (TGF-β1) levels. A statistically non-significant difference (P < 0.005) between the AML patients and control group with regard to the expression of CD33, CD11b, and HLA-DR was observed. Analysis of CD33 expression in myeloid-derived suppressor cells (MDSCs) showed a significant decrease in the proportion of CD33 positive MDSC cells in isolated peripheral blood samples (88.078 ± 1.284). Also, the expression of CD11b in MDSC cells was high (98.841±1.935) in MDSC cells. The mean level of IFN-γ (pg/ml) increased in AML in compared to control group (9.202 ± 0.244), (7.906±1.22), respectively. While TGF- β1 (pg/ml) concentration was found to be elevated in AML patients (69.04 ± 9.92) compared to control group (33.884 ± 2.888). In conclusion, circulating MDSCs were significantly elevated in peripheral blood of patients with AML and characterized by the CD33+CD11b + phenotype; TGF-β1 and IFN-γ can be released in the presence of native human AML cells and affect AML cell proliferation and evasion from immune system.

Keywords

Main Subjects

Biology

References

[1] R. M. Shallis, R. Wang, A. Davidoff, X. Ma, and A. M. Zeidan, “Epidemiology of acute myeloid leukemia: Recent progress and enduring challenges,” Blood Rev., vol. 36, pp. 70–87, 2019.

[2] C. Roma-Rodrigues, R. Mendes, P. V. Baptista, and A. R. Fernandes, “Targeting tumor microenvironment for cancer therapy,” Int. J. Mol. Sci., vol. 20, no. 4, 2019.

[3] A. J. Lamble and E. F. Lind, “Targeting the immune microenvironment in acute myeloid leukemia: A focus on T cell immunity,” Front. Oncol., vol. 8, no. JUN, pp. 1–13, 2018.

[4] C. S. Hong et al., “Circulating exosomes carrying an immunosuppressive cargo interfere with cellular immunotherapy in acute myeloid leukemia,” Sci. Rep., vol. 7, no. 1, pp. 1–10, 2017.

[5] S. Ostrand-Rosenberg and C. Fenselau, “Myeloid-Derived Suppressor Cells: Immune-Suppressive Cells That Impair Antitumor Immunity and Are Sculpted by Their Environment,” J. Immunol., vol. 200, no. 2, pp. 422–431, 2018.

[6] C. M. Diaz-Montero, J. Finke, and A. J. Montero, “Myeloid-derived suppressor cells in cancer: Therapeutic, predictive, and prognostic implications,” Semin. Oncol., vol. 41, no. 2, pp. 174–184, 2014.

[7] V. Fleming et al., “Targeting myeloid-derived suppressor cells to bypass tumor-induced immunosuppression,” Front. Immunol., vol. 9, no. MAR, 2018.

[8] T. M. Grzywa et al., “Myeloid Cell-Derived Arginase in Cancer Immune Response,” Front. Immunol., vol. 11, no. May, pp. 1–24, 2020.

[9] I. R. Ramachandran et al., “Bone marrow PMN-MDSCs and neutrophils are functionally similar in protection of multiple myeloma from chemotherapy,” Cancer Lett., vol. 371, no. 1, pp. 117–124, 2016.

[10] A. R. Pyzer et al., “MUC1-mediated induction of myeloid-derived suppressor cells in patients with acute myeloid leukemia,” Blood, vol. 129, no. 13, pp. 1791–1801, 2017.

[11] M. D. Tabernero et al., “Adult precursor B-ALL with BCR/ABL gene rearrangements displays a unique immunophenotype based on the pattern of CD10, CD34, CD13 and CD38 expression,” Leukemia, vol. 15, no. 3, pp. 406–414, 2001.

[12] J. M. Jaso, S. A. Wang, J. L. Jorgensen, and P. Lin, “Multi-color flow cytometric immunophenotyping for detection of minimal residual disease in AML: past, present and future,” Bone Marrow Transplant., vol. 49, no. 9, pp. 1129–1138, 2014.

[13] M. Sade-Feldman et al., “Clinical significance of circulating CD33+ CD11bHLA-DR myeloid cells in patients with stage IV melanoma treated with ipilimumab,” Clin. Cancer Res., vol. 22, no. 23, pp. 5661–5672, 2016.

[14] S. Budhwar, P. Verma, R. Verma, S. Rai, and K. Singh, “The Yin and Yang of myeloid derived suppressor cells,” Front. Immunol., vol. 9, no. NOV, pp. 1–16, 2018.

[15] I. Azzaoui et al., “T-cell defect in diffuse large B-cell lymphomas involves expansion of myeloid-derived suppressor cells,” Blood, vol. 128, no. 8, pp. 1081–1092, 2016.

[16] S. Mahnaz, L. D. Roy, M. Bose, C. De, S. Nath, and P. Mukherjee, “Repression of MUC1 promotes expansion and suppressive function of myeloid-derived suppressor cells in pancreatic ductal adenocarcinoma and breast cancer murine models,” bioRxiv, pp. 1–15, 2020.

[17] H. Sun et al., “Increase in myeloid-derived suppressor cells (MDSCs) associated with minimal residual disease (MRD) detection in adult acute myeloid leukemia,” Int. J. Hematol., vol. 102, no. 5, pp. 579–586, 2015.

[18] F. R. Appelbaum and I. D. Bernstein, “Gemtuzumab ozogamicin for acute myeloid leukemia,” Blood, vol. 130, no. 22, pp. 2373–2376, 2017.

[19] L. Fenwarth et al., “Biomarkers of gemtuzumab ozogamicin response for acute myeloid leukemia treatment,” Int. J. Mol. Sci., vol. 21, no. 16, pp. 1–21, 2020.

[20] M. S. de Propris et al., “High CD33 expression levels in acute myeloid leukemia cells carrying the nucleophosmin (NPM1) mutation,” Haematologica, vol. 96, no. 10, pp. 1548–1551, 2011.

[21] L. W. M. M. Terstappen, Z. Hollander, H. Meiners, and M. R. Loken, “Quantitative comparison of myeloid antigens on five lineages of mature peripheral blood cells,” J. Leukoc. Biol., vol. 48, no. 2, pp. 138–148, 1990.

[22] I. Jilani et al., “Differences in CD33 intensity between various myeloid neoplasms,” Am. J. Clin. Pathol., vol. 118, no. 4, pp. 560–566, 2002.

[23] M. G. Lechner, D. J. Liebertz, and A. L. Epstein, “Correction: Characterization of Cytokine-Induced Myeloid-Derived Suppressor Cells from Normal Human Peripheral Blood Mononuclear Cells,” J. Immunol., vol. 185, no. 9, pp. 5668–5668, 2010.

[24] W. Shang, Y. Gao, Z. Tang, Y. Zhang, and R. Yang, “The pseudogene OLFR29-PS1 promotes the suppressive function and differentiation of monocytic MDSCs,” Cancer Immunol. Res., vol. 7, no. 5, pp. 813–827, 2019.

[25] Y. Wang, J. Roller, M. D. Menger, and H. Thorlacius, “Sepsis-induced leukocyte adhesion in the pulmonary microvasculature in vivo is mediated by CD11a and CD11b,” Eur. J. Pharmacol., vol. 702, no. 1–3, pp. 135–141, 2013.

[26] C. Ding et al., “Integrin CD11b negatively regulates BCR signalling to maintain autoreactive B cell tolerance,” Nat. Commun., vol. 4, 2013.

[27] G. S. Ling et al., “Integrin CD11b positively regulates TLR4-induced signalling pathways in dendritic cells but not in macrophages,” Nat. Commun., vol. 5, pp. 1–12, 2014.

[28] I. Antohe et al., “B7-Positive and B7-Negative Acute Myeloid Leukemias Display Distinct T Cell Maturation Profiles, Immune Checkpoint Receptor Expression, and European Leukemia Net Risk Profiles,” Front. Oncol., vol. 10, no. March, pp. 1–12, 2020.

[29] I. Lodewijckx and J. Cools, “Deregulation of the interleukin-7 signaling pathway in lymphoid malignancies,” Pharmaceuticals, vol. 14, no. 5, 2021.

[30] K. Fatehchand et al., “Interferon-γ promotes antibody-mediated fratricide of acute myeloid leukemia cells,” J. Biol. Chem., vol. 291, no. 49, pp. 25656–25666, 2016.

[31] C. B. Childs, J. A. Proper, R. F. Tucker, and H. L. Moses, “Serum contains a platelet-derived transforming growth factor.,” Proc. Natl. Acad. Sci. U. S. A., vol. 79, no. 17, pp. 5312–5316, 1982.

[32] D. Wotton and J. Massague, “Transcriptional control by the TGF- b / Smad signaling system,” EMBO J., vol. 19, no. 8, pp. 1745–1754, 2000.

[33] B. G. Kim, E. Malek, S. H. Choi, J. J. Ignatz-Hoover, and J. J. Driscoll, “Novel therapies emerging in oncology to target the TGF-β pathway,” J. Hematol. Oncol., vol. 14, no. 1, pp. 1–20, 2021.

Journal of University of Anbar for Pure Science

Evaluation The Role of CD33+ CD11b+ myeloid-derived Suppressor Cells in Patients With AML

References

References

Volume 16, Issue 1 - Issue Serial Number 1
July 2022
Page 1-8

Evaluation The Role of CD33+ CD11b+ myeloid-derived Suppressor Cells in Patients With AML

References

References

Volume 16, Issue 1 - Issue Serial Number 1July 2022Page 1-8

Volume 16, Issue 1 - Issue Serial Number 1
July 2022
Page 1-8