The role of Galectin-3 in modulating tumor growth and immunosuppression within the tumor microenvironment

Farhad, Mohammad; Rolig, Annah S.; Redmond, William L.

doi:10.1080/2162402x.2018.1434467

Cited by 150 publications

(144 citation statements)

References 53 publications

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“…To the best of our knowledge, endostatin or GAL3BP have not been reported as markers for treatment efficacy during immunotherapy in melanoma or other cancers. However, a galectin 3 inhibitor, in combination with ipilimumab or PD‐1 inhibition, is being currently evaluated for the treatment of patients with metastatic melanoma underscoring that galectin 3 or its marker Gal3BP (as well as endostatin) could be part of a panel of biomarkers that predicts the outcome for immunotherapy in melanoma. Our data suggest endostatin and Gal3BP as potential prognostic biomarkers for ipilimumab in MM.…”

Section: Discussionmentioning

confidence: 99%

Prognostic biomarkers for immunotherapy with ipilimumab in metastatic melanoma

Nyakas

Aamdal

Jacobsen

et al. 2019

Clinical and Experimental Immunology

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Summary New therapies, including the anti‐cytotoxic T lymphocyte antigen (CTLA)‐4 antibody, ipilimumab, is approved for metastatic melanoma. Prognostic biomarkers need to be identified, because the treatment has serious side effects. Serum samples were obtained before and during treatment from 56 patients with metastatic or unresectable malignant melanoma, receiving treatment with ipilimumab in a national Phase IV study (NCT0268196). Expression of a panel of 17 inflammatory‐related markers reflecting different pathways including extracellular matrix remodeling and fibrosis, vascular inflammation and monocyte/macrophage activation were measured at baseline and the second and/or third course of treatment with ipilimumab. Six candidate proteins [endostatin, osteoprotegerin (OPG), C‐reactive protein (CRP), pulmonary and activation‐regulated chemokine (PARC), growth differentiation factor 15 (GDF15) and galectin‐3 binding‐protein (Gal3BP)] were persistently higher in non‐survivors. In particular, high Gal3BP and endostatin levels were also independently associated with poor 2‐year survival after adjusting for lactate dehydrogenase, M‐stage and number of organs affected. A 1 standard deviation increase in endostatin gave 1·74 times [95% confidence interval (CI) = 1·10–2·78, P = 0·019] and for Gal3BP 1·52 times (95% CI = 1·01–2·29, P = 0·047) higher risk of death in the adjusted model. Endostatin and Gal3BP may represent prognostic biomarkers for patients on ipilimumab treatment in metastatic melanoma and should be further evaluated. Owing to the non‐placebo design, we could only relate our findings to prognosis during ipilimumab treatment.

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Section: Discussionmentioning

confidence: 99%

Prognostic biomarkers for immunotherapy with ipilimumab in metastatic melanoma

Nyakas

Aamdal

Jacobsen

et al. 2019

Clinical and Experimental Immunology

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“…Heart disease acute heart failure plasma level combination with natriuretic peptide [62] acute heart failure plasma level promising prognostic marker [63] chronic heart failure plasma level useful in HF patients with preserved LVEF [64] chronic heart failure myocardial and plasma level not associated with histology [65] acute myocardial infarction serum level no definite relationship with ventricular remodeling [66] Nervous system diseases myelin degeneration tissues activation of the phagocytosis of degenerated myelin [42] intracerebral hemorrhage plasma level prognostic predictor [67] subarachnoid hemorrhage plasma level prognostic predictor [68] global brain ischemia cerebrospinal fluid prognostic marker and inflammatory mediator [69] Renal disease CKD plasma level associated with progression of CKD [25] SLE nephritis serum and biopsy specimens associated with SLE patients, particularly in SLE nephritis [70] Liver disease liver fibrosis serum Gal-3 related binding protein assessing liver fibrosis [71] Connective tissue diseases rheumatoid arthritis serum level increased in early rheumatoid arthritis [72] SLE serum anti-Gal-3 antibody a key role in SLE skin lesions [73] systemic sclerosis serum level predictor of mortality [74] Neoplasms colorectal cancer serum and tissues related to tumor progression [52] breast cancer human cell lines important factor for treatment [75] non-small cell lung cancer tumor expression promotion of invasion and metastasis [76] lung and prostate cancers tumor expression therapeutic target of tumor immunity [77] cervical cancer tumor expression targets of multifunctional cancer treatment [78] thyroid cancer tumor expression diagnostic marker [79]…”

Section: Diseasesmentioning

confidence: 99%

Galectin-3 as a Next-Generation Biomarker for Detecting Early Stage of Various Diseases

et al. 2020

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Galectin-3 is a β-galactoside-binding lectin which is important in numerous biological activities in various organs, including cell proliferation, apoptotic regulation, inflammation, fibrosis, and host defense. Galectin-3 is predominantly located in the cytoplasm and expressed on the cell surface, and then often secreted into biological fluids, like serum and urine. It is also released from injured cells and inflammatory cells under various pathological conditions. Many studies have revealed that galectin-3 plays an important role as a diagnostic or prognostic biomarker for certain types of heart disease, kidney disease, viral infection, autoimmune disease, neurodegenerative disorders, and tumor formation. In particular, it has been recognized that galectin-3 is extremely useful for detecting many of these diseases in their early stages. The purpose of this article is to review and summarize the recent literature focusing on the biomarker characteristics and long-term outcome predictions of galectin-3, in not only patients with various types of diseases, but associated animal models.

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“…Galectins have already been shown to be proteins involved in controlling immune responses in a broad range of diseases (28,38). Most reports on cancer have concentrated on Gal-1 and its effect on immune escape, but it must be emphasized that different galectin members can have different and sometimes opposite effects on T cell behavior (20).…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, the downregulation of full-length Gal-3 observed in patients apparently matches neither with the definition of Gal-3 as a marker of PCa tumor cell aggressiveness nor with poor marker prognosis for PCa patients (30)(31)(32). However, because Gal-3 controls the functions of a variety of antitumor immune cells (33)(34)(35)(36)(37)(38), we decided to further investigate its role in antitumor immune responses. With the goal to transfer our results to clinics, we paid special attention to conditions where a chemotherapy treatment is associated with vaccination since results from clinical trials have shown that Docetaxel-based chemotherapy could promote the effectiveness of immunotherapy in a variety of cancers (39)(40)(41)(42)(43)(44) as well as in PCa patients (45)(46).…”

Section: Introductionmentioning

confidence: 95%

Galectin-3 as a new negative checkpoint of the immune response is the key target for effective immunotherapy against prostate cancer

Tiraboschi

Gentilini

Jaworski

et al. 2019

Preprint

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Keywords: Active immunotherapy; combined treatment; preclinical model; drug new effect.Galectin-3 is the key immunological check-point responsible of the failure of immunotherapies protocols against prostate cancer and could be controlled by Docetaxelbased chemotherapy prior to vaccination. AbstractProstate cancer (PCa) is a major health problem worldwide. Taxol derivatives-based chemotherapies or immunotherapies are usually proposed depending on the symptomatic status. In the case of immunotherapy, tumors develop robust immune escape mechanisms that abolish any protective response. However, Docetaxel has been shown to enhance the effectiveness of immunotherapy in a variety of cancers, but to date, the mechanism is still unknown. Herein, we showed first that Galectin-3 (Gal-3) expressed by prostate tumor cells is the principal immunological checkpoint responsible of the failure of immunotherapy; and that Docetaxel leads to the inhibition of Gal-3 expression in PCa cells as well as in clinical samples of mCRPC patients promoting a Th1 response. We thus optimized a prostate cancer animal model that undergoes surgical resection of the tumor like prostatectomy to mimic what is usually performed in patients. More importantly, using low and nontoxic doses of taxane prior to immunotherapy, we were able to directly impact the activation and proliferation of CD8+ cytotoxic T cells through reducing the number of CD8+CD122+CD28-T cells and highly control tumor recurrence. Thus, Gal-3 expression by PCa cells is a key inhibitor for the success of immunotherapy, and low doses of Docetaxel with noncytotoxic effect on leukocyte survival should be used prior to vaccination for all PCa patients. This combined treatment sequence right after surgery would promote the preconditioning of the tumor microenvironment, allowing for effective anti-tumor immunotherapy and can be transferred rapidly to clinical therapeutic protocols.

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The role of Galectin-3 in modulating tumor growth and immunosuppression within the tumor microenvironment

Cited by 150 publications

References 53 publications

Prognostic biomarkers for immunotherapy with ipilimumab in metastatic melanoma

Prognostic biomarkers for immunotherapy with ipilimumab in metastatic melanoma

Galectin-3 as a Next-Generation Biomarker for Detecting Early Stage of Various Diseases

Galectin-3 as a new negative checkpoint of the immune response is the key target for effective immunotherapy against prostate cancer

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