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Article ; Online: Phosphatidylserine externalization as immune checkpoint in cancer.

Kur, Ivan-Maximiliano / Weigert, Andreas

Pflugers Archiv : European journal of physiology

2024

Abstract: Cancer is the second leading cause of mortality worldwide. Despite recent advances in cancer treatment including immunotherapy with immune checkpoint inhibitors, new unconventional biomarkers and targets for the detection, prognosis, and treatment of ... ...

Abstract	Cancer is the second leading cause of mortality worldwide. Despite recent advances in cancer treatment including immunotherapy with immune checkpoint inhibitors, new unconventional biomarkers and targets for the detection, prognosis, and treatment of cancer are still in high demand. Tumor cells are characterized by mutations that allow their unlimited growth, program their local microenvironment to support tumor growth, and spread towards distant sites. While a major focus has been on altered tumor genomes and proteomes, crucial signaling molecules such as lipids have been underappreciated. One of these molecules is the membrane phospholipid phosphatidylserine (PS) that is usually found at cytosolic surfaces of cellular membranes but can be rapidly and massively shuttled to the extracellular leaflet of the plasma membrane during apoptosis to serve as a limiting factor for immune responses. These immunosuppressive interactions are exploited by tumor cells to evade the immune system. In this review, we describe mechanisms of immune regulation in tumors, discuss if PS may constitute an inhibitory immune checkpoint, and describe current and future strategies for targeting PS to reactivate the tumor-associated immune system.
Language	English
Publishing date	2024-04-04
Publishing country	Germany
Document type	Journal Article ; Review
ZDB-ID	6380-0
ISSN	1432-2013 ; 0031-6768
ISSN (online)	1432-2013
ISSN	0031-6768
DOI	10.1007/s00424-024-02948-7
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Article ; Online: Immune modulation through secretory autophagy.

Weigert, Andreas / Herhaus, Lina

Journal of cellular biochemistry

2023

Abstract: Autophagy is a central mechanism of cellular homeostasis through the degradation of a wide range of cellular constituents. However, recent evidence suggests that autophagy actively provides information to neighboring cells via a process called secretory ... ...

Abstract	Autophagy is a central mechanism of cellular homeostasis through the degradation of a wide range of cellular constituents. However, recent evidence suggests that autophagy actively provides information to neighboring cells via a process called secretory autophagy. Secretory autophagy couples the autophagy machinery to the secretion of cellular content via extracellular vesicles (EVs). EVs carry a variety of cargo, that reflect the pathophysiological state of the originating cells and have the potential to change the functional profile of recipient cells, to modulate cell biology. The immune system has evolved to maintain local and systemic homeostasis. It is able to sense a wide array of molecules signaling disturbed homeostasis, including EVs and their content. In this review, we explore the emerging concept of secretory autophagy as a means to communicate cellular, and in total tissue pathophysiological states to the immune system to initiate the restoration of tissue homeostasis. Understanding how autophagy mediates the secretion of immunogenic factors may hold great potential for therapeutic intervention.
Language	English
Publishing date	2023-06-01
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	392402-6
ISSN	1097-4644 ; 0730-2312
ISSN (online)	1097-4644
ISSN	0730-2312
DOI	10.1002/jcb.30427
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Article ; Online: Heterogeneity of tertiary lymphoid structures in cancer.

You, Xin / Koop, Kristina / Weigert, Andreas

Frontiers in immunology

2023 Volume 14, Page(s) 1286850

Abstract: The success of immunotherapy approaches, such as immune checkpoint blockade and cellular immunotherapy with genetically modified lymphocytes, has firmly embedded the immune system in the roadmap for combating cancer. Unfortunately, the majority of cancer ...

Abstract	The success of immunotherapy approaches, such as immune checkpoint blockade and cellular immunotherapy with genetically modified lymphocytes, has firmly embedded the immune system in the roadmap for combating cancer. Unfortunately, the majority of cancer patients do not yet benefit from these therapeutic approaches, even when the prognostic relevance of the immune response in their tumor entity has been demonstrated. Therefore, there is a justified need to explore new strategies for inducing anti-tumor immunity. The recent connection between the formation of ectopic lymphoid aggregates at tumor sites and patient prognosis, along with an effective anti-tumor response, suggests that manipulating the occurrence of these tertiary lymphoid structures (TLS) may play a critical role in activating the immune system against a growing tumor. However, mechanisms governing TLS formation and a clear understanding of their substantial heterogeneity are still lacking. Here, we briefly summarize the current state of knowledge regarding the mechanisms driving TLS development, outline the impact of TLS heterogeneity on clinical outcomes in cancer patients, and discuss appropriate systems for modeling TLS heterogeneity that may help identify new strategies for inducing protective TLS formation in cancer patients.
MeSH term(s)	Humans ; Tertiary Lymphoid Structures ; Tumor Microenvironment ; Neoplasms ; Prognosis ; Lymphocytes, Tumor-Infiltrating
Language	English
Publishing date	2023-12-04
Publishing country	Switzerland
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2023.1286850
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Book ; Online ; Thesis: The influence of IL-38 in the process of B cell differentiation

Wilmes, Christian [Verfasser] / Weigert, Andreas [Akademischer Betreuer] / Weigert, Andreas [Gutachter] / Mühl, Heiko [Gutachter]

2023

Author's details	Christian Wilmes ; Gutachter: Andreas Weigert, Heiko Mühl ; Betreuer: Andreas Weigert
Keywords	Medizin, Gesundheit ; Medicine, Health
Subject code	sg610
Language	English
Publisher	Universitätsbibliothek Johann Christian Senckenberg
Publishing place	Frankfurt am Main
Document type	Book ; Online ; Thesis
Database	Digital theses on the web

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Article ; Online: Breast Cancer CAFs: Spectrum of Phenotypes and Promising Targeting Avenues.

Elwakeel, Eiman / Weigert, Andreas

International journal of molecular sciences

2021 Volume 22, Issue 21

Abstract: Activationof the tumor-associated stroma to support tumor growth is a common feature observed in different cancer entities. This principle is exemplified by cancer-associated fibroblasts (CAFs), which are educated by the tumor to shape its development ... ...

Abstract	Activationof the tumor-associated stroma to support tumor growth is a common feature observed in different cancer entities. This principle is exemplified by cancer-associated fibroblasts (CAFs), which are educated by the tumor to shape its development across all stages. CAFs can alter the extracellular matrix (ECM) and secrete a variety of different molecules. In that manner they have the capability to affect activation, survival, proliferation, and migration of other stromal cells and cancer cell themselves. Alteration of the ECM, desmoplasia, is a common feature of breast cancer, indicating a prominent role for CAFs in shaping tumor development in the mammary gland. In this review, we summarize the multiple roles CAFs play in mammary carcinoma. We discuss experimental and clinical strategies to interfere with CAFs function in breast cancer. Moreover, we highlight the issues arising from CAFs heterogeneity and the need for further research to identify CAFs subpopulation(s) that can be targeted to improve breast cancer therapy.
MeSH term(s)	Animals ; Breast Neoplasms/pathology ; Cancer-Associated Fibroblasts/pathology ; Extracellular Matrix/pathology ; Female ; Humans ; Phenotype ; Tumor Microenvironment/physiology
Language	English
Publishing date	2021-10-27
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms222111636
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Keep a Little Fire Burning-The Delicate Balance of Targeting Sphingosine-1-Phosphate in Cancer Immunity.

Olesch, Catherine / Brüne, Bernhard / Weigert, Andreas

International journal of molecular sciences

2022 Volume 23, Issue 3

Abstract: The sphingolipid sphingosine-1-phosphate (S1P) promotes tumor development through a variety of mechanisms including promoting proliferation, survival, and migration of cancer cells. Moreover, S1P emerged as an important regulator of tumor ... ...

Abstract	The sphingolipid sphingosine-1-phosphate (S1P) promotes tumor development through a variety of mechanisms including promoting proliferation, survival, and migration of cancer cells. Moreover, S1P emerged as an important regulator of tumor microenvironmental cell function by modulating, among other mechanisms, tumor angiogenesis. Therefore, S1P was proposed as a target for anti-tumor therapy. The clinical success of current cancer immunotherapy suggests that future anti-tumor therapy needs to consider its impact on the tumor-associated immune system. Hereby, S1P may have divergent effects. On the one hand, S1P gradients control leukocyte trafficking throughout the body, which is clinically exploited to suppress auto-immune reactions. On the other hand, S1P promotes pro-tumor activation of a diverse range of immune cells. In this review, we summarize the current literature describing the role of S1P in tumor-associated immunity, and we discuss strategies for how to target S1P for anti-tumor therapy without causing immune paralysis.
MeSH term(s)	Animals ; Humans ; Immune System/metabolism ; Inflammation/immunology ; Lysophospholipids/immunology ; Lysophospholipids/metabolism ; Neoplasms/immunology ; Neoplasms/metabolism ; Neovascularization, Pathologic/immunology ; Signal Transduction/physiology ; Sphingolipids/metabolism ; Sphingolipids/physiology ; Sphingosine/analogs & derivatives ; Sphingosine/immunology ; Sphingosine/metabolism ; Tumor Microenvironment/physiology
Chemical Substances	Lysophospholipids ; Sphingolipids ; sphingosine 1-phosphate (26993-30-6) ; Sphingosine (NGZ37HRE42)
Language	English
Publishing date	2022-01-24
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms23031289
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Article ; Online: Long-Term Trends in the Protection Against Severe Courses of COVID-19 by Vaccination.

Beyerlein, Andreas / Weigert, Maximilian / Katz, Katharina / Küchenhoff, Helmut / Hartl, Wolfgang

Deutsches Arzteblatt international

2023 Volume 120, Issue 51-52, Page(s) 873–878

Abstract: Background: The long-term course of protection against severe COVID-19 courses by vaccine-induced or hybrid immunity in Germany is unclear.: Methods: We studied 146 457 cases aged 60-99 years in the German federal state of Bavaria who were immunized ... ...

Abstract	Background: The long-term course of protection against severe COVID-19 courses by vaccine-induced or hybrid immunity in Germany is unclear. Methods: We studied 146 457 cases aged 60-99 years in the German federal state of Bavaria who were immunized against COVID-19 and tested positive for it from February 2022 to January 2023. We calculated adjusted hazard ratios for a severe course (hospitalization or death due to COVID-19) for different intervals between the onset of full primary or booster immunity and the date of the infection. Results: 3342 (2.3%) severe courses of COVID-19 were observed in the first 60 days after the infection. The risk of a severe course rose with the interval between the onset of immune protection and the infection (adjusted hazard ratios and 95% confidence intervals at 6, 9, 12, and 15 months: 1.14 [1.08; 1.20]; 1.33 [1.24; 1.42]; 1.39 [1.25; 1.54]; 1.61 [1.35; 1.93]). The risk rose more slowly when mRNA-based vaccines were used exclusively. In a previous study, we observed 82% initial efficacy in cases aged 60 and above who received a booster vaccination (compared to unvaccinated cases) and an absolute risk reduction of 2.1%. If one extrapolates these findings to the current study, the residual efficacy and absolute risk reduction are found to be approximately 71% and 1.8% (respectively) at 6 months, and 32% and 0.8% at 15 months. Conclusion: These results indicate that, during the Omicron wave, the protection of older persons against a severe COVID-19 course gradually declined from six months after vaccination onward. The limitations of this study include confounders that could not be taken into account, possible misclassification of the cause of death, and selection bias due to missing information about vaccination status and severe COVID-19 courses.
MeSH term(s)	Humans ; Aged ; Aged, 80 and over ; COVID-19/epidemiology ; COVID-19/prevention & control ; Vaccination ; Cluster Analysis ; Germany/epidemiology ; Hospitalization
Language	English
Publishing date	2023-11-14
Publishing country	Germany
Document type	Observational Study
ZDB-ID	2406159-1
ISSN	1866-0452 ; 1866-0452
ISSN (online)	1866-0452
ISSN	1866-0452
DOI	10.3238/arztebl.m2023.0230
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Article ; Online: Breast Cancer CAFs

Eiman Elwakeel / Andreas Weigert

International Journal of Molecular Sciences, Vol 22, Iss 11636, p

Spectrum of Phenotypes and Promising Targeting Avenues

2021 Volume 11636

Abstract: Activation of the tumor-associated stroma to support tumor growth is a common feature observed in different cancer entities. This principle is exemplified by cancer-associated fibroblasts (CAFs), which are educated by the tumor to shape its development ... ...

Abstract	Activation of the tumor-associated stroma to support tumor growth is a common feature observed in different cancer entities. This principle is exemplified by cancer-associated fibroblasts (CAFs), which are educated by the tumor to shape its development across all stages. CAFs can alter the extracellular matrix (ECM) and secrete a variety of different molecules. In that manner they have the capability to affect activation, survival, proliferation, and migration of other stromal cells and cancer cell themselves. Alteration of the ECM, desmoplasia, is a common feature of breast cancer, indicating a prominent role for CAFs in shaping tumor development in the mammary gland. In this review, we summarize the multiple roles CAFs play in mammary carcinoma. We discuss experimental and clinical strategies to interfere with CAFs function in breast cancer. Moreover, we highlight the issues arising from CAFs heterogeneity and the need for further research to identify CAFs subpopulation(s) that can be targeted to improve breast cancer therapy.
Keywords	cancer-associated fibroblasts ; mammary carcinoma ; cancer ; tumor microenvironment ; extracellular matrix ; metastasis ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	610
Language	English
Publishing date	2021-10-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Prostaglandin E

Hog, Pauline / Kuntschar, Silvia / Rappl, Peter / Huard, Arnaud / Weigert, Andreas / Brüne, Bernhard / Schmid, Tobias

Biology

2023 Volume 12, Issue 11

Abstract: Macrophages are a highly versatile and heterogenic group of immune cells, known for their involvement in inflammatory reactions. However, our knowledge about distinct subpopulations of macrophages and their specific contribution to the resolution of ... ...

Abstract	Macrophages are a highly versatile and heterogenic group of immune cells, known for their involvement in inflammatory reactions. However, our knowledge about distinct subpopulations of macrophages and their specific contribution to the resolution of inflammation remains incomplete. We have previously shown, in an in vivo peritonitis model, that inhibition of the synthesis of the pro-inflammatory lipid mediator prostaglandin E
Language	English
Publishing date	2023-11-16
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2661517-4
ISSN	2079-7737
ISSN	2079-7737
DOI	10.3390/biology12111441
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Book ; Online ; Thesis: Role of mPGES-1-derived PGE2 in activation of breast cancer stromal fibroblasts

Elwakeel, Eiman [Verfasser] / Weigert, Andreas [Akademischer Betreuer] / Weigert, Andreas [Gutachter] / Geißlinger, Gerd [Gutachter]

2022

Author's details	Eiman Elwakeel ; Gutachter: Andreas Weigert, Gerd Geißlinger ; Betreuer: Andreas Weigert
Keywords	Biowissenschaften, Biologie ; Life Science, Biology
Subject code	sg570
Language	English
Publisher	Universitätsbibliothek Johann Christian Senckenberg
Publishing place	Frankfurt am Main
Document type	Book ; Online ; Thesis
Database	Digital theses on the web

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