Galectin‐9 and myeloid‐derived suppressor cell as prognostic indicators for chronic lymphocytic leukemia

Abstract Background Galectin‐9 and myeloid‐derived suppressor cells (MDSCs) have an important role in tumors, but their clinical values in chronic lymphocytic leukemia (CLL) have not been fully elucidated. This study aimed to analyze the prognosis values of Galectin‐9 and MDSCs in CLL. Methods The concentrations of Galectin‐9, argininase‐1, and inducible nitric oxide synthase in serum were detected by enzyme‐linked immune sorbent assay. The expression of Tim‐3 protein in peripheral blood mononuclear cell was detected by Western blot. Flow cytometry was used to analyze the percentages of Tim‐3 on T‐cells (CD3+T, CD4+T, and CD8+T cells) and MDSCs. Results Our results showed that Galectin‐9 and MDSCs significantly increased in CLL patients and were closely related to the disease progression. Patient's receiver operating characteristic, progression‐free survival, and Cox regression analysis showed that Galectin9 and MDSCs were poor prognostic factors of CLL. Conclusion Galectin‐9 and MDSCs were associated with clinical progression and could be important prognostic indicators for CLL.

[1]  Peitao Zhang,et al.  Targeting myeloid derived suppressor cells reverts immune suppression and sensitizes BRAF-mutant papillary thyroid cancer to MAPK inhibitors , 2022, Nature Communications.

[2]  M. Aghaei,et al.  Galectin-9 inhibits cell proliferation and induces apoptosis in Jurkat and KE-37 acute lymphoblastic leukemia cell lines via caspase-3 activation , 2021, Research in pharmaceutical sciences.

[3]  N. Pang,et al.  Activated Galectin‐9/Tim3 promotes Treg and suppresses Th1 effector function in chronic lymphocytic leukemia , 2021, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[4]  K. Stamatopoulos,et al.  Myeloid-derived suppressor cell subtypes differentially influence T-cell function, T-helper subset differentiation, and clinical course in CLL , 2021, Leukemia.

[5]  P. Dessen,et al.  Serial transplantation unmasks galectin-9 contribution to tumor immune escape in the MB49 murine model , 2021, Scientific Reports.

[6]  P. Rodriguez,et al.  Tumor-related stress regulates functional plasticity of MDSCs. , 2021, Cellular immunology.

[7]  N. Tumino,et al.  Interaction Between MDSC and NK Cells in Solid and Hematological Malignancies: Impact on HSCT , 2021, Frontiers in Immunology.

[8]  N. Pang,et al.  The role of Tim‐3/Galectin‐9 pathway in T‐cell function and prognosis of patients with human papilloma virus‐associated cervical carcinoma , 2021, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[9]  Jun Yao,et al.  Galectin-9 interacts with PD-1 and TIM-3 to regulate T cell death and is a target for cancer immunotherapy , 2021, Nature Communications.

[10]  John E. Mullinax,et al.  Tumor interferon signaling and suppressive myeloid cells associate with CAR T cell failure in large B cell lymphoma. , 2021, Blood.

[11]  R. Tandon,et al.  Galectin-9 as a biomarker of disease severity. , 2021, Cellular immunology.

[12]  Ihor O. Arkhypov,et al.  IL-6 as a major regulator of MDSC activity and possible target for cancer immunotherapy. , 2020, Cellular immunology.

[13]  N. Pang,et al.  [TIM-3/galectin-9 is involved in negative regulation of T cells in patients with chronic lymphocytic leukemia]. , 2020, Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology.

[14]  J. Cui,et al.  Galectin-9 promotes a suppressive microenvironment in human cancer by enhancing STING degradation , 2020, Oncogenesis.

[15]  S. Molica,et al.  Prognostic models for chronic lymphocytic leukemia (CLL): a systematic review and meta-analysis , 2020, Leukemia.

[16]  Y. Miyagi,et al.  Galectin-9 expression as a poor prognostic factor in patients with renal cell carcinoma , 2020, Cancer Immunology, Immunotherapy.

[17]  C. Klein,et al.  Leukemia-induced dysfunctional TIM-3+CD4+ bone marrow T cells increase risk of relapse in pediatric B-precursor ALL patients , 2020, Leukemia.

[18]  D. Aust,et al.  Detection of pancreatic ductal adenocarcinoma with galectin-9 serum levels , 2020, Oncogene.

[19]  G. Kristiansen,et al.  Molecular and immune correlates of TIM-3 (HAVCR2) and galectin 9 (LGALS9) mRNA expression and DNA methylation in melanoma , 2019, Clinical Epigenetics.

[20]  M. Hallek.  Chronic lymphocytic leukemia: 2020 update on diagnosis, risk stratification and treatment , 2019, American journal of hematology.

[21]  M. Sugaya,et al.  Possible therapeutic applicability of galectin-9 in cutaneous T-cell lymphoma. , 2019, Journal of dermatological science.

[22]  L. Varani,et al.  The Tim-3-Galectin-9 Pathway and Its Regulatory Mechanisms in Human Breast Cancer , 2019, Front. Immunol..

[23]  X. Zhang,et al.  Immuno-subtyping of breast cancer reveals distinct myeloid cell profiles and immunotherapy resistance mechanisms , 2019, Nature Cell Biology.

[24]  T. Greten,et al.  Targeting the crosstalk between cytokine-induced killer cells and myeloid-derived suppressor cells in hepatocellular carcinoma. , 2019, Journal of hepatology.

[25]  J. Chudek,et al.  Increased serum levels of Galectin-9 in patients with chronic lymphocytic leukemia , 2018, Oncology letters.

[26]  R. Tesi.  MDSC; the Most Important Cell You Have Never Heard Of. , 2019, Trends in pharmacological sciences.

[27]  S. Malek,et al.  Chronic Lymphocytic Leukemia , 2019, Methods in Molecular Biology.

[28]  Y. Bi,et al.  ZAP-70 in chronic lymphocytic leukemia: A meta-analysis. , 2018, Clinica chimica acta; international journal of clinical chemistry.

[29]  T. Niki,et al.  MicroRNA profiles during galectin-9-induced apoptosis of pancreatic cancer cells. , 2017, Oncology letters.

[30]  D. Gabrilovich,et al.  Myeloid-derived suppressor cells coming of age , 2018, Nature Immunology.

[31]  Yih-Leong Chang,et al.  The immunologic advantage of recurrent nasopharyngeal carcinoma from the viewpoint of Galectin-9/Tim-3-related changes in the tumour microenvironment , 2017, Scientific Reports.

[32]  L. Varani,et al.  The Tim-3-galectin-9 Secretory Pathway is Involved in the Immune Escape of Human Acute Myeloid Leukemia Cells , 2017, EBioMedicine.

[33]  S. Dagdas,et al.  CD38 Expression and Variation as a Prognostic Factor Chronic Lymphocytic Leukemia. , 2016, Clinical laboratory.

[34]  P. Oefner,et al.  CLL-cells induce IDOhi CD14+HLA-DRlo myeloid-derived suppressor cells that inhibit T-cell responses and promote TRegs. , 2014, Blood.

[35]  B. Hoerni,et al.  [Treatment of chronic lymphocytic leukemia]. , 1971, Bordeaux medical.