Different Expression Pattern of TIM-3 and Galectin-9 Molecules by Peripheral and Peritoneal Lymphocytes in Women with and without Endometriosis

Meggyes, Mátyás; Szereday, László; Bohonyi, Noémi; Koppán, Miklós; Szegedi, Sarolta; Marics-Kutas, Anna; Marton, Mirjam; Totsimon, Anett; Polgar, Beata

doi:10.3390/ijms21072343

Cited by 12 publications

(18 citation statements)

References 58 publications

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“…When Tim-3 on NK cells bind to its ligands, its function of secreting cytokines and killing target cells is diminished (20)(21)(22). It has been assumed that the Tim-3-Galectin-9 pathway plays an important role in regulating tumor cells escaping from immune surveillance (23,24). In our study, of all the Tim-3 ligands, only CEACAM1 was expressed on NK-92 cells (about 70%).…”

Section: Nk Cells Are An Important Part Of Innate Immunity and Can Di...mentioning

confidence: 56%

Tim-3 Blockade Elicits Potent Anti-Multiple Myeloma Immunity of Natural Killer Cells

Wen

Jiang

et al. 2022

Front. Oncol.

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Multiple myeloma (MM) is still an incurable plasma cell tumor. Natural killer (NK) cells are characterized by efficient anti-tumor activity, and their activity is one basis of cancer immunotherapeutic strategies. Tim-3, one of the immune checkpoint molecules, negatively regulates NK cell activity. To evaluate roles of the Tim-3 pathway blocking in the regulation of NK cell mediated- anti-MM activity in vitro and in vivo, anti-Tim-3 and/or anti-its ligand (HMGB1, CEACAM1 or Galetin-9) antibodies were applied respectively to block the Tim-3 pathway in the present study. Our results showed that Tim-3 was highly expressed on NK cells, in particular on in vitro expanded NK (exNK) cells. NK cells with Tim-3 blockade displayed a significantly higher degranulation and cytolytic activity against both human MM cell lines and primary MM cells, compared to the isotype control antibody-treated NK cells. The increased NK cell cytolytic activity by Tim-3 blocking was associated with up-regulation of cytotoxicity-related molecules, including perforin, granzyme B, TNF-α and IFN-γ. Ligand (HMGB1, CEACAM1 or Galetin-9) expression on MM cells was at different levels, and accordingly, the improvement in NK cell-mediated killing activity by different ligand blocking were also varying. Tim-3 blocking showed much more efficient enhancement of NK cell cytolytic activity than its ligand blockings. More importantly, exNK cells with Tim-3 blockade significantly inhibited MM tumor growth and prolonged the survival of MM-bearing NOD/SCID mice. Our results also showed that NK cells from peripheral blood and bone marrow of MM patients expressed much higher levels of Tim-3 than their counterparts from controls. Taken together, Tim-3 may be an important target molecule used for developing an antibody and/or NK cell based immunotherapeutic strategies for MM.

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Section: Nk Cells Are An Important Part Of Innate Immunity and Can Di...mentioning

confidence: 56%

Tim-3 Blockade Elicits Potent Anti-Multiple Myeloma Immunity of Natural Killer Cells

Wen

Jiang

et al. 2022

Front. Oncol.

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“…The immunoregulatory function of Gal-9, its substantial increase during pathologic conditions, and its association with disease severity have been shown previously ( 31 , 32 ). Meggyes et al have also shown an altered pathway for expression of Gal-9 on peripheral blood and fluid lymphocytes of women with endometriosis, compared to those without the disorder, which confirms the role of Gal-9 in the impaired immunologic mechanism of endometriosis ( 33 ). According to the fact that endometriosis is an inflammatory disease that stimulates immune response and inflammation in the body ( 34 ) with numerous immunologic and inflammatory changes ( 35 ), the response to immunologic conditions is mainly impaired in women with endometriosis.…”

Section: Discussionmentioning

confidence: 76%

The Diagnostic Accuracy of Galectin-9 for Diagnosis of Endometriosis in Comparison with Laparoscopy

Jarollahi¹,

Chaichian²,

Jarollahi³

et al. 2022

JRI

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Background: Endometriosis is a common devastating gynecological disease with severe complications. Researches on noninvasive diagnostic tests with acceptable accuracy are still ongoing. The purpose of the present study was to evaluate the diagnostic value of serum Galectin-9 (Gal-9) level in comparison with laparoscopic results in endometriosis patients. Methods: Sixty-one patients, referred to Booali, Rasool-e-Akram, and Pars Hospitals affiliated to Islamic Azad University of Medical Sciences, were recruited. Patients laparoscopically diagnosed with endometriosis were assigned to the case (n=32) and who diagnosed with other diseases were assigned to the control group (n=29). In general, 56 patients (30 in case and 26 in control group) completed the study. The serum level of Galectin-9 was measured using ELISA method before laparoscopy and was compared between the groups. Next, categorical variables were compared using Chi square and quantitative variables using independent samples t test or Mann-Whitney U test. The Gal-9 cut-off was calculated using the Youden’s index and ROC curve; then, sensitivity, specificity, positive and negative predictive value, and positive and negative likelihood ratio of Gal-9 were reported. The p<0.05 were considered statistically significant. Results: Mean serum level of Galectin-9 was 669.3±416.50 pg/ml in the case group and 265.42±492.30 pg/ml in the control group (p=0.001). Considering a cut-off value of 138 pg/ml, Galectin-9 had a sensitivity of 100% and specificity of 88.46% for diagnosis of endometriosis (p<0.001). Conclusion: Galectin-9 measurement is helpful in diagnosis of endometriosis. Future studies are recommended for investigating the generalizability of these results.

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“…They established the elevated expression of Gal-9 on CD4 + T cells and Tregs in the PB of EMS patients in comparison to healthy subjects. Additionally, the authors demonstrated a higher expression of Gal-9 on the peritoneal CD8 + T cells and NK cells compared with the PB [ 26 ]. Moreover, peritoneal T cell subsets showed an increased TIM-3 expression than in the PB.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, peritoneal T cell subsets showed an increased TIM-3 expression than in the PB. The authors also revealed elevated TIM-3 expression on peritoneal NKT-like cells in the EMS group [ 26 ]. Confronting the literature data with our findings, we suggest that the accumulation of Gal-9 expressing mDCs and pDCs in the peritoneal cavity could represent the hallmark of the immune regulation in women with endometriosis.…”

Section: Discussionmentioning

confidence: 99%

Expression of Gal-9 on Dendritic Cells and Soluble Forms of TIM-3/Gal-9 in Patients Suffering from Endometriosis

Suszczyk

Skiba

Pawłowska

et al. 2023

IJMS

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Immune system dysregulation is clinically evident in the pathogenesis of endometriosis (EMS). Changes in the dendritic cells (DCs) activity or phenotype may be involved in the implantation and growth of endometrial tissue outside the uterus in the disease. The TIM-3/Gal-9 axis is implicated in the development of immune tolerance. However, the knowledge about the exact role of this pathway in the EMS is extremely poor. In the present study, we evaluated the expression of Gal-9 on myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) in the peripheral blood (PB) and peritoneal fluid (PF) of both EMS patients (n = 82) and healthy subjects (n = 10) via flow cytometry. We also investigated the concentrations of soluble Gal-9 and TIM-3 in the plasma and PF of EMS patients and the control group using ELISA. We showed significantly elevated percentages of mDCs-Gal-9+ and pDCs-Gal-9+, and significantly higher concentrations of the soluble form of Gal-9 and TIM-3 in the PF of EMS patients than in circulation. Our results led us to conclude that the accumulation of Gal-9 expressing mDCs and pDCs in the PF and high sTIM-3/Gal-9 production in the peritoneal cavity could represent the hallmark of immune regulation in EMS patients, which may augment the inflammatory process and development/maintenance of local immunosuppression.

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Different Expression Pattern of TIM-3 and Galectin-9 Molecules by Peripheral and Peritoneal Lymphocytes in Women with and without Endometriosis

Cited by 12 publications

References 58 publications

Tim-3 Blockade Elicits Potent Anti-Multiple Myeloma Immunity of Natural Killer Cells

Tim-3 Blockade Elicits Potent Anti-Multiple Myeloma Immunity of Natural Killer Cells

The Diagnostic Accuracy of Galectin-9 for Diagnosis of Endometriosis in Comparison with Laparoscopy

Expression of Gal-9 on Dendritic Cells and Soluble Forms of TIM-3/Gal-9 in Patients Suffering from Endometriosis

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