Elevated Galectin-3 levels in the tumor microenvironment of ovarian cancer – implication of ROS mediated suppression of NK cell antitumor response via tumor-associated neutrophils
IntroductionOvarian cancer is a lethal disease with low survival rates for women diagnosed in advanced stages. Current cancer immunotherapies are not efficient in ovarian cancer, and there is therefore a significant need for novel treatment options. The β-galactoside-binding lectin, Galectin-3, is i...
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Frontiers Media S.A.
2024-12-01
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1506236/full |
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| author | Veronika Karlsson Veronika Karlsson Ebba Stål Emma Stoopendahl Anton Ivarsson Hakon Leffler Maria Lycke Martina Sundqvist Karin Sundfeldt Karin Sundfeldt Karin Christenson Elin Bernson Elin Bernson |
| author_facet | Veronika Karlsson Veronika Karlsson Ebba Stål Emma Stoopendahl Anton Ivarsson Hakon Leffler Maria Lycke Martina Sundqvist Karin Sundfeldt Karin Sundfeldt Karin Christenson Elin Bernson Elin Bernson |
| author_sort | Veronika Karlsson |
| collection | DOAJ |
| description | IntroductionOvarian cancer is a lethal disease with low survival rates for women diagnosed in advanced stages. Current cancer immunotherapies are not efficient in ovarian cancer, and there is therefore a significant need for novel treatment options. The β-galactoside-binding lectin, Galectin-3, is involved in different immune processes and has been associated with poor outcome in various cancer diagnoses. Here, we investigated how Galectin-3 affects the interaction between natural killer (NK) cells and neutrophils in the tumor microenvironment of ovarian cancer.MethodAscites from the metastatic tumor microenvironment and cyst fluid from the primary tumor site were collected from patients with high-grade serous carcinoma (HGSC) together with peripheral blood samples. Galectin-3 concentration was measured in ascites, cyst fluid and serum or plasma. Neutrophils isolated from HGSC ascites and autologous blood were analyzed to evaluate priming status and production of reactive oxygen species. In vitro co-culture assays with NK cells, neutrophils and K562 target cells (cancer cell line) were conducted to evaluate NK cell viability, degranulation and cytotoxicity.ResultsHigh levels of Galectin-3 were observed in cyst fluid and ascites from patients with HGSC. Neutrophils present in HGSC ascites showed signs of priming; however, the priming status varied greatly among the patient samples. Galectin-3 induced production of reactive oxygen species in ascites neutrophils, but only from a fraction of the patient samples, which is in line with the heterogenous priming status of the ascites neutrophils. In co-cultures with NK cells and K562 target cells, we observed that Galectin-3-induced production of reactive oxygen species in neutrophils resulted in decreased NK cell viability and lowered anti-tumor responses.ConclusionTaken together, our results demonstrate high levels of Galectin-3 in the tumormicroenvironment of HGSC. High levels of Galectin-3 may induce production of reactiveoxygen species in ascites neutrophils in some patients. In turn, reactive oxygen species produced by neutrophils may modulate the NK cell anti-tumor immunity. Together, this study suggests further investigation to evaluate if a Galectin-3-targeting therapy may be used in ovarian cancer. |
| format | Article |
| id | doaj-art-4e8a9f73531d47249dbfce3917a12d0f |
| institution | DOAJ |
| issn | 1664-3224 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj-art-4e8a9f73531d47249dbfce3917a12d0f2025-08-20T02:52:13ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-12-011510.3389/fimmu.2024.15062361506236Elevated Galectin-3 levels in the tumor microenvironment of ovarian cancer – implication of ROS mediated suppression of NK cell antitumor response via tumor-associated neutrophilsVeronika Karlsson0Veronika Karlsson1Ebba Stål2Emma Stoopendahl3Anton Ivarsson4Hakon Leffler5Maria Lycke6Martina Sundqvist7Karin Sundfeldt8Karin Sundfeldt9Karin Christenson10Elin Bernson11Elin Bernson12Sahlgrenska Center for Cancer Research, University of Gothenburg, Gothenburg, SwedenDepartment of Oral Microbiology and Immunology, Institute of Odontology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, SwedenSahlgrenska Center for Cancer Research, University of Gothenburg, Gothenburg, SwedenSahlgrenska Center for Cancer Research, University of Gothenburg, Gothenburg, SwedenSahlgrenska Center for Cancer Research, University of Gothenburg, Gothenburg, SwedenDepartment of Laboratory Medicine, Lund University, Lund, SwedenDepartment of Obstetrics and Gynecology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, SwedenDepartment of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, SwedenSahlgrenska Center for Cancer Research, University of Gothenburg, Gothenburg, SwedenDepartment of Obstetrics and Gynecology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, SwedenDepartment of Oral Microbiology and Immunology, Institute of Odontology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, SwedenSahlgrenska Center for Cancer Research, University of Gothenburg, Gothenburg, SwedenDepartment of Obstetrics and Gynecology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, SwedenIntroductionOvarian cancer is a lethal disease with low survival rates for women diagnosed in advanced stages. Current cancer immunotherapies are not efficient in ovarian cancer, and there is therefore a significant need for novel treatment options. The β-galactoside-binding lectin, Galectin-3, is involved in different immune processes and has been associated with poor outcome in various cancer diagnoses. Here, we investigated how Galectin-3 affects the interaction between natural killer (NK) cells and neutrophils in the tumor microenvironment of ovarian cancer.MethodAscites from the metastatic tumor microenvironment and cyst fluid from the primary tumor site were collected from patients with high-grade serous carcinoma (HGSC) together with peripheral blood samples. Galectin-3 concentration was measured in ascites, cyst fluid and serum or plasma. Neutrophils isolated from HGSC ascites and autologous blood were analyzed to evaluate priming status and production of reactive oxygen species. In vitro co-culture assays with NK cells, neutrophils and K562 target cells (cancer cell line) were conducted to evaluate NK cell viability, degranulation and cytotoxicity.ResultsHigh levels of Galectin-3 were observed in cyst fluid and ascites from patients with HGSC. Neutrophils present in HGSC ascites showed signs of priming; however, the priming status varied greatly among the patient samples. Galectin-3 induced production of reactive oxygen species in ascites neutrophils, but only from a fraction of the patient samples, which is in line with the heterogenous priming status of the ascites neutrophils. In co-cultures with NK cells and K562 target cells, we observed that Galectin-3-induced production of reactive oxygen species in neutrophils resulted in decreased NK cell viability and lowered anti-tumor responses.ConclusionTaken together, our results demonstrate high levels of Galectin-3 in the tumormicroenvironment of HGSC. High levels of Galectin-3 may induce production of reactiveoxygen species in ascites neutrophils in some patients. In turn, reactive oxygen species produced by neutrophils may modulate the NK cell anti-tumor immunity. Together, this study suggests further investigation to evaluate if a Galectin-3-targeting therapy may be used in ovarian cancer.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1506236/fullgalectin-3ovarian cancerNK cellsneutrophilstumor immunologyROS release |
| spellingShingle | Veronika Karlsson Veronika Karlsson Ebba Stål Emma Stoopendahl Anton Ivarsson Hakon Leffler Maria Lycke Martina Sundqvist Karin Sundfeldt Karin Sundfeldt Karin Christenson Elin Bernson Elin Bernson Elevated Galectin-3 levels in the tumor microenvironment of ovarian cancer – implication of ROS mediated suppression of NK cell antitumor response via tumor-associated neutrophils Frontiers in Immunology galectin-3 ovarian cancer NK cells neutrophils tumor immunology ROS release |
| title | Elevated Galectin-3 levels in the tumor microenvironment of ovarian cancer – implication of ROS mediated suppression of NK cell antitumor response via tumor-associated neutrophils |
| title_full | Elevated Galectin-3 levels in the tumor microenvironment of ovarian cancer – implication of ROS mediated suppression of NK cell antitumor response via tumor-associated neutrophils |
| title_fullStr | Elevated Galectin-3 levels in the tumor microenvironment of ovarian cancer – implication of ROS mediated suppression of NK cell antitumor response via tumor-associated neutrophils |
| title_full_unstemmed | Elevated Galectin-3 levels in the tumor microenvironment of ovarian cancer – implication of ROS mediated suppression of NK cell antitumor response via tumor-associated neutrophils |
| title_short | Elevated Galectin-3 levels in the tumor microenvironment of ovarian cancer – implication of ROS mediated suppression of NK cell antitumor response via tumor-associated neutrophils |
| title_sort | elevated galectin 3 levels in the tumor microenvironment of ovarian cancer implication of ros mediated suppression of nk cell antitumor response via tumor associated neutrophils |
| topic | galectin-3 ovarian cancer NK cells neutrophils tumor immunology ROS release |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1506236/full |
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