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Article ; Online: Tumor Pigmentation Does Not Affect Light-Activated Belzupacap Sarotalocan Treatment but Influences Macrophage Polarization in a Murine Melanoma Model.

Ma, Sen / Huis In't Veld, Ruben V / Hao, Yang / Gu, Zili / Rich, Cadmus / Gelmi, Maria Chiara / Mulder, Aat A / van Veelen, Peter A / Vu, T Khanh H / van Hall, Thorbald / Ossendorp, Ferry A / Jager, Martine J

Investigative ophthalmology & visual science

2024 Volume 65, Issue 1, Page(s) 42

Abstract: Purpose: Pigmentation in uveal melanoma is associated with increased malignancy and is known as a barrier for photodynamic therapy. We investigated the role of pigmentation in tumor behavior and the response to light-activated Belzupacap sarotalocan ( ... ...

Abstract	Purpose: Pigmentation in uveal melanoma is associated with increased malignancy and is known as a barrier for photodynamic therapy. We investigated the role of pigmentation in tumor behavior and the response to light-activated Belzupacap sarotalocan (Bel-sar) treatment in a pigmented (wild type) and nonpigmented (tyrosinase knock-out [TYR knock-out]) cell line in vitro and in a murine model. Methods: The B16F10 (TYR knock-out) was developed using CRISPR/Cas9. After the treatment with light-activated Bel-sar, cytotoxicity and exposure of damage-associated molecular patterns (DAMPs) were measured by flow cytometry. Treated tumor cells were co-cultured with bone marrow-derived macrophages (BMDMs) and dendritic cells (DCs) to assess phagocytosis and activation. Both cell lines were injected subcutaneously in syngeneic C57BL/6 mice. Results: Knock-out of the tyrosinase gene in B16F10 led to loss of pigmentation and immature melanosomes. Pigmented tumors contained more M1 and fewer M2 macrophages compared with amelanotic tumors. Bel-sar treatment induced near complete cell death, accompanied with enhanced exposure of DAMPs in both cell lines, resulting in enhanced phagocytosis of BMDMs and maturation of DCs. Bel-sar treatment induced a shift to M1 macrophages and delayed tumor growth in both in vivo tumor models. Following treatment, especially the pigmented tumors and their draining lymph nodes contained IFN-gamma positive CD8+T cells. Conclusions: Pigmentation influenced the type of infiltrating macrophages in the tumor, with more M1 macrophages in pigmented tumors. Belzupacap sarotalocan treatment induced immunogenic cell death and tumor growth delay in pigmented as well as in nonpigmented models and stimulated M1 macrophage influx in both models.
MeSH term(s)	Animals ; Mice ; Melanoma/genetics ; Monophenol Monooxygenase/metabolism ; Mice, Inbred C57BL ; Macrophages/metabolism ; Pigmentation
Chemical Substances	Monophenol Monooxygenase (EC 1.14.18.1)
Language	English
Publishing date	2024-01-25
Publishing country	United States
Document type	Journal Article
ZDB-ID	391794-0
ISSN	1552-5783 ; 0146-0404
ISSN (online)	1552-5783
ISSN	0146-0404
DOI	10.1167/iovs.65.1.42
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Article ; Online: Normal Pregnancy-Induced Islet Beta Cell Proliferation in Mouse Models That Are Deficient in Serotonin-Signaling.

Goyvaerts, Lotte / Schraenen, Anica / Lemaire, Katleen / Veld, Peter In't / Smolders, Ilse / Maroteaux, Luc / Schuit, Frans

International journal of molecular sciences

2022 Volume 23, Issue 24

Abstract: During mouse pregnancy placental lactogens stimulate prolactin receptors on pancreatic islet beta cells to induce expression of the tryptophan ... ...

Abstract	During mouse pregnancy placental lactogens stimulate prolactin receptors on pancreatic islet beta cells to induce expression of the tryptophan hydroxylase
Language	English
Publishing date	2022-12-13
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms232415816
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Article ; Online: Rodent versus human insulitis: why the huge disconnect?

in't Veld, Peter

Current opinion in endocrinology, diabetes, and obesity

2015 Volume 22, Issue 2, Page(s) 86–90

Abstract: Purpose of review: The purpose of this article is to summarize recent developments in the histopathology of recent-onset type 1 diabetes.: Recent findings: Insulitis is considered to be the defining lesion in young type 1 diabetic patients, and ... ...

Abstract	Purpose of review: The purpose of this article is to summarize recent developments in the histopathology of recent-onset type 1 diabetes. Recent findings: Insulitis is considered to be the defining lesion in young type 1 diabetic patients, and insight into its pathogenic mechanism is crucial for the development of effective new therapies. The present overview highlights some recent developments including an international consensus guideline for the diagnosis of insulitis in type 1 diabetic patients, immunophenotyping of the insulitic lesions, evidence for a heterogeneity of the disease process and a discussion on the differences and similarities between insulitis in patients and in rodent models of the disease. Summary: We have reviewed recent data, published over the last year, on the nature and mechanism of insulitis in both patients and the nonobese diabetic mouse model.
MeSH term(s)	Animals ; Autoimmunity ; Diabetes Mellitus, Type 1/blood ; Diabetes Mellitus, Type 1/diagnosis ; Diabetes Mellitus, Type 1/immunology ; Diabetes Mellitus, Type 1/physiopathology ; Disease Models, Animal ; Humans ; Mice, Inbred NOD ; Pancreas/immunology ; Pancreas/metabolism ; Pancreas/physiopathology ; Prognosis ; Species Specificity ; T-Lymphocytes/immunology ; T-Lymphocytes/metabolism ; Translational Medical Research
Language	English
Publishing date	2015-04
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2272017-0
ISSN	1752-2978 ; 1752-296X
ISSN (online)	1752-2978
ISSN	1752-296X
DOI	10.1097/MED.0000000000000135
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Article: The β2-adrenergic receptor in the apical membrane of intestinal enterocytes senses sugars to stimulate glucose uptake from the gut.

Paulussen, Frederik / Kulkarni, Chetan P / Stolz, Frank / Lescrinier, Eveline / De Graeve, Stijn / Lambin, Suzan / Marchand, Arnaud / Chaltin, Patrick / In't Veld, Peter / Mebis, Joseph / Tavernier, Jan / Van Dijck, Patrick / Luyten, Walter / Thevelein, Johan M

Frontiers in cell and developmental biology

2023 Volume 10, Page(s) 1041930

Abstract: The presence of sugar in the gut causes induction of SGLT1, the sodium/glucose cotransporter in intestinal epithelial cells (enterocytes), and this is accompanied by stimulation of sugar absorption. Sugar sensing was suggested to involve a G-protein ... ...

Abstract	The presence of sugar in the gut causes induction of SGLT1, the sodium/glucose cotransporter in intestinal epithelial cells (enterocytes), and this is accompanied by stimulation of sugar absorption. Sugar sensing was suggested to involve a G-protein coupled receptor and cAMP - protein kinase A signalling, but the sugar receptor has remained unknown. We show strong expression and co-localization with SGLT1 of the β2-adrenergic receptor (
Language	English
Publishing date	2023-01-09
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2737824-X
ISSN	2296-634X
ISSN	2296-634X
DOI	10.3389/fcell.2022.1041930
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Article ; Online: Insulitis in human type 1 diabetes: a comparison between patients and animal models.

In't Veld, Peter

Seminars in immunopathology

2014 Volume 36, Issue 5, Page(s) 569–579

Abstract: Human type 1 diabetes (T1D) is considered to be an autoimmune disease, with CD8+ T-cell-mediated ...

Abstract	Human type 1 diabetes (T1D) is considered to be an autoimmune disease, with CD8+ T-cell-mediated cytotoxicity being directed against the insulin-producing beta cells, leading to a gradual decrease in beta cell mass and the development of chronic hyperglycemia. The histopathologically defining lesion in recent-onset T1D patients is insulitis, a relatively subtle leucocytic infiltration present in approximately 10% of the islets of Langerhans from children with recent-onset (<1 year) disease. Due to the transient nature of the infiltrate, its heterogeneous distribution in the pancreas and the nature of the patient population, material for research is extremely rare and limited to a cumulative total of approximately 150 cases collected over the past century. Most studies on the etiopathogenesis of T1D have therefore focused on the non-obese diabetic (NOD) mouse model, which shares many genetic and immunological disease characteristics with human T1D, although its islet histopathology is remarkably different. In view of these differences and in view of the limited success of clinical immune interventions based on observations in the NOD mouse, there is a renewed focus on studying the pathogenetic process in patient material.
MeSH term(s)	Animals ; Autoimmunity ; Diabetes Mellitus, Type 1/etiology ; Diabetes Mellitus, Type 1/pathology ; Disease Models, Animal ; Humans ; Inflammation/immunology ; Inflammation/pathology ; Islets of Langerhans/immunology ; Islets of Langerhans/pathology ; Mice ; Mice, Inbred NOD
Language	English
Publishing date	2014-07-09
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2316828-6
ISSN	1863-2300 ; 1863-2297
ISSN (online)	1863-2300
ISSN	1863-2297
DOI	10.1007/s00281-014-0438-4
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Article ; Online: The dark side of islet vasculature.

In't Veld, Peter / Lammert, Eckhard

Diabetologia

2014 Volume 58, Issue 1, Page(s) 4–6

MeSH term(s)	Animals ; Blood Vessels/pathology ; Graft Survival ; Islets of Langerhans/blood supply ; Islets of Langerhans Transplantation/pathology ; Male
Language	English
Publishing date	2014-10-18
Publishing country	Germany
Document type	Journal Article ; Comment
ZDB-ID	1694-9
ISSN	1432-0428 ; 0012-186X
ISSN (online)	1432-0428
ISSN	0012-186X
DOI	10.1007/s00125-014-3418-2
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Article ; Online: Insulitis and lymphoid structures in the islets of Langerhans of a 66-year-old patient with long-standing type 1 diabetes.

Smeets, Silke / Staels, Willem / Stangé, Geert / Gillard, Pieter / De Leu, Nico / In't Veld, Peter

Virchows Archiv : an international journal of pathology

2020 Volume 478, Issue 6, Page(s) 1209–1214

Abstract: Insulitis is a characteristic inflammatory lesion consisting of immune cell infiltrates around and within the pancreatic islets of patients with recent-onset type 1 diabetes (T1D). The infiltration is typically mild, both in terms of the number of ... ...

Abstract	Insulitis is a characteristic inflammatory lesion consisting of immune cell infiltrates around and within the pancreatic islets of patients with recent-onset type 1 diabetes (T1D). The infiltration is typically mild, both in terms of the number of infiltrating cells and the number of islets affected. Here, we present an unusual histopathological case study of a 66-year-old female patient with long-standing T1D, insulitis, and islet-associated lymphoid tissue. Most islets in the head of the pancreas of this patient were insulin-deficient, whereas the islets in the tail appeared normal. Insulitis was present in 0.84% of the insulin-containing islets and three islets had large lymphocytic infiltrates resembling tertiary lymphoid structures (TLS). Of note, this is the first description of potential TLS in the endocrine pancreas of a patient with T1D. Their association with a marked residual beta cell mass is of interest and may hint at new insights into disease progression and regulation of autoimmunity.
MeSH term(s)	Aged ; Autoimmunity/immunology ; Diabetes Mellitus, Type 1/complications ; Diabetes Mellitus, Type 1/immunology ; Diabetes Mellitus, Type 1/pathology ; Disease Progression ; Female ; Humans ; Insulin/metabolism ; Islets of Langerhans/immunology ; Islets of Langerhans/pathology ; Lymph Nodes/immunology ; Lymph Nodes/pathology
Chemical Substances	Insulin
Language	English
Publishing date	2020-08-24
Publishing country	Germany
Document type	Case Reports ; Journal Article
ZDB-ID	1184867-4
ISSN	1432-2307 ; 0945-6317
ISSN (online)	1432-2307
ISSN	0945-6317
DOI	10.1007/s00428-020-02915-4
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Article ; Online: Insulitis in human type 1 diabetes: The quest for an elusive lesion.

In't Veld, Peter

Islets

2011 Volume 3, Issue 4, Page(s) 131–138

Abstract: ... in early stage disease in children. A cytotoxic T-cell mediated destruction of insulin-producing β-cells is ...

Abstract	The histopathology of type 1 diabetes is defined by a decreased β-cell mass in association with insulitis, a characteristic lymphocytic infiltration limited to the islets of Langerhans and prominent in early stage disease in children. A cytotoxic T-cell mediated destruction of insulin-producing β-cells is thought to be initiated by an unknown (auto)antigen, leading to the destruction > 75% of β-cell mass at clinical diagnosis. Although considered to be pathognomonic for recent onset disease, insulitis has only been described in approximately 150 cases over the past century. This review describes the quest for this elusive lesion and gives its incidence in various patient subpopulations stratified for age of onset and duration of the disease. It discusses recent new insights into the regenerative capacity of the β-cell mass in the pre-clinical stages of the disease and relates these findings to the inflammatory processes within the islet tissue.
MeSH term(s)	Adolescent ; Adult ; Age of Onset ; Child ; Child, Preschool ; Diabetes Mellitus, Type 1/etiology ; Diabetes Mellitus, Type 1/immunology ; History, 20th Century ; History, 21st Century ; Humans ; Infant ; Islets of Langerhans/pathology ; Lymphocytes/immunology ; Organ Size ; Pancreatitis/epidemiology ; Pancreatitis/history ; Pancreatitis/pathology ; Pancreatitis/physiopathology ; Young Adult
Language	English
Publishing date	2011-07-01
Publishing country	United States
Document type	Historical Article ; Journal Article ; Research Support, Non-U.S. Gov't ; Review
ISSN	1938-2022
ISSN (online)	1938-2022
DOI	10.4161/isl.3.4.15728
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Article: Combinatorial Therapeutic Approaches with Nanomaterial-Based Photodynamic Cancer Therapy.

Hao, Yang / Chung, Chih Kit / Yu, Zhenfeng / Huis In 't Veld, Ruben V / Ossendorp, Ferry A / Ten Dijke, Peter / Cruz, Luis J

Pharmaceutics

2022 Volume 14, Issue 1

Abstract: Photodynamic therapy (PDT), in which a light source is used in combination with a photosensitizer to induce local cell death, has shown great promise in therapeutically targeting primary tumors with negligible toxicity and minimal invasiveness. However, ... ...

Abstract	Photodynamic therapy (PDT), in which a light source is used in combination with a photosensitizer to induce local cell death, has shown great promise in therapeutically targeting primary tumors with negligible toxicity and minimal invasiveness. However, numerous studies have shown that noninvasive PDT alone is not sufficient to completely ablate tumors in deep tissues, due to its inherent shortcomings. Therefore, depending on the characteristics and type of tumor, PDT can be combined with surgery, radiotherapy, immunomodulators, chemotherapy, and/or targeted therapy, preferably in a patient-tailored manner. Nanoparticles are attractive delivery vehicles that can overcome the shortcomings of traditional photosensitizers, as well as enable the codelivery of multiple therapeutic drugs in a spatiotemporally controlled manner. Nanotechnology-based combination strategies have provided inspiration to improve the anticancer effects of PDT. Here, we briefly introduce the mechanism of PDT and summarize the photosensitizers that have been tested preclinically for various cancer types and clinically approved for cancer treatment. Moreover, we discuss the current challenges facing the combination of PDT and multiple cancer treatment options, and we highlight the opportunities of nanoparticle-based PDT in cancer therapies.
Language	English
Publishing date	2022-01-04
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527217-2
ISSN	1999-4923
ISSN	1999-4923
DOI	10.3390/pharmaceutics14010120
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Article ; Online: Insulitis in the pancreas of non-diabetic organ donors under age 25 years with multiple circulating autoantibodies against islet cell antigens.

Smeets, Silke / De Paep, Diedert Luc / Stangé, Geert / Verhaeghen, Katrijn / Van der Auwera, Bart / Keymeulen, Bart / Weets, Ilse / Ling, Zhidong / In't Veld, Peter / Gorus, Frans

Virchows Archiv : an international journal of pathology

2021 Volume 479, Issue 2, Page(s) 295–304

Abstract: ... T-cells. Islets with insulitis were found in close proximity to islets devoid of insulin-positivity ...

Abstract	Autoantibodies against islet cell antigens are routinely used to identify subjects at increased risk of symptomatic type 1 diabetes, but their relation to the intra-islet pathogenetic process that leads to positivity for these markers is poorly understood. We screened 556 non-diabetic organ donors (3 months to 24 years) for five different autoantibodies and found positivity in 27 subjects, 25 single- and two double autoantibody-positive donors. Histopathological screening of pancreatic tissue samples showed lesion characteristic for recent-onset type 1 diabetes in the two organ donors with a high-risk profile, due to their positivity for multiple autoantibodies and HLA-inferred risk. Inflammatory infiltrates (insulitis) were found in a small fraction of islets (<5%) and consisted predominantly of CD3+CD8+ T-cells. Islets with insulitis were found in close proximity to islets devoid of insulin-positivity; such pseudo-atrophic islets were present in multiple small foci scattered throughout the pancreatic tissue or were found to be distributed with a lobular pattern. Relative beta cell area in both single and multiple autoantibody-positive donors was comparable to that in autoantibody-negative controls. In conclusion, in organ donors under age 25 years, insulitis and pseudo-atrophic islets were restricted to multiple autoantibody-positive individuals allegedly at high risk of developing symptomatic type 1 diabetes, in line with reports in older age groups. These observations may give further insight into the early pathogenetic events that may culminate in clinically overt disease.
MeSH term(s)	Adolescent ; Age Factors ; Antigens/immunology ; Autoantibodies/blood ; Biomarkers/blood ; CD8-Positive T-Lymphocytes/immunology ; Case-Control Studies ; Cell Proliferation ; Child ; Child, Preschool ; Diabetes Mellitus, Type 1/blood ; Diabetes Mellitus, Type 1/immunology ; Diabetes Mellitus, Type 1/pathology ; Donor Selection ; Female ; Humans ; Infant ; Insulin-Secreting Cells/immunology ; Insulin-Secreting Cells/pathology ; Islets of Langerhans Transplantation ; Male ; Tissue Donors ; Young Adult
Chemical Substances	Antigens ; Autoantibodies ; Biomarkers
Language	English
Publishing date	2021-02-16
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1184867-4
ISSN	1432-2307 ; 0945-6317
ISSN (online)	1432-2307
ISSN	0945-6317
DOI	10.1007/s00428-021-03055-z
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