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Your search keyword '"Ligia I, Bastea"' showing total 5 results
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5 results on '"Ligia I, Bastea"'

1. Inflammatory and alternatively activated macrophages independently induce metaplasia but cooperatively drive pancreatic precancerous lesion growth

Author

Geou-Yarh Liou, Alicia K. Fleming Martinez, Heike R. Döppler, Ligia I. Bastea, and Peter Storz

Subjects
Cancer, Cell biology, Immunology, Molecular biology, Science
Abstract

Summary: The innate immune system has a key role in pancreatic cancer initiation, but the specific contribution of different macrophage populations is still ill-defined. While inflammatory (M1) macrophages have been shown to drive acinar-to-ductal metaplasia (ADM), a cancer initiating event, alternatively activated (M2) macrophages have been attributed to lesion growth and fibrosis. Here, we determined cytokines and chemokines secreted by both macrophage subtypes. Then, we analyzed their role in ADM initiation and lesion growth, finding that while M1 secrete TNF, CCL5, and IL-6 to drive ADM, M2 induce this dedifferentiation process via CCL2, but the effects are not additive. This is because CCL2 induces ADM by generating ROS and upregulating EGFR signaling, thus using the same mechanism as cytokines from inflammatory macrophages. Therefore, while effects on ADM are not additive between macrophage polarization types, both act synergistically on the growth of low-grade lesions by activating different MAPK pathways.

Published
2023
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2. Ym1+ macrophages orchestrate fibrosis, lesion growth, and progression during development of murine pancreatic cancer

Author

Alicia K. Fleming Martinez, Heike R. Döppler, Ligia I. Bastea, Brandy H. Edenfield, Geou-Yarh Liou, and Peter Storz

Subjects
Microenvironment, Immunology, Cancer, Science
Abstract

Summary: Desmoplasia around pancreatic lesions is a barrier for immune cells and a hallmark of developing and established pancreatic cancer. However, the contribution of the innate immune system to this process is ill-defined. Using the KC mouse model and primary cells in vitro, we show that alternatively activated macrophages (AAM) crosstalk with pancreatic lesion cells and pancreatic stellate cells (PSCs) to mediate fibrosis and progression of lesions. TGFβ1 secreted by AAM not only drives activation of quiescent PSCs but also in activated PSCs upregulates expression of TIMP1, a factor previously shown as crucial in fibrosis. Once activated, PSCs auto-stimulate proliferation via CXCL12. Furthermore, we found that TIMP1/CD63 signaling mediates PanIN lesion growth and TGFβ1 contributes to a cadherin switch and drives structural collapse of lesions, indicating a potential progression step. Taken together, our data indicate TGFβ1 produced by Ym1+ AAM as a major driver of processes that initiate the development of pancreatic cancer.

Published
2022
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3. Data from Pomalidomide Alters Pancreatic Macrophage Populations to Generate an Immune-Responsive Environment at Precancerous and Cancerous Lesions

Author

Peter Storz, Han W. Tun, John A. Copland, Brandy Edenfield, Yushi Qiu, Zhimin Li, Heike Doeppler, Christina A. von Roemeling, Alicia K. Fleming, Veethika Pandey, Geou-Yarh Liou, and Ligia I. Bastea

Abstract

During development of pancreatic cancer, alternatively activated macrophages contribute to fibrogenesis, pancreatic intraepithelial neoplasia (PanIN) lesion growth, and generation of an immunosuppressive environment. Here, we show that the immunomodulatory agent pomalidomide depletes pancreatic lesion areas of alternatively activated macrophage populations. Pomalidomide treatment resulted in downregulation of interferon regulatory factor 4, a transcription factor for M2 macrophage polarization. Pomalidomide-induced absence of alternatively activated macrophages led to a decrease in fibrosis at PanIN lesions and in syngeneic tumors; this was due to generation of an inflammatory, immune-responsive environment with increased expression of IL1α and presence of activated (IFNγ-positive) CD4+ and CD8+ T-cell populations. Our results indicate that pomalidomide could be used to decrease fibrogenesis in pancreatic cancer and may be ideal as a combination treatment with chemotherapeutic drugs or other immunotherapies.Significance:These findings reveal new insights into how macrophage populations within the pancreatic cancer microenvironment can be modulated, providing the means to turn the microenvironment from immunosuppressive to immune-responsive.

Published
2023

4. Supplementary Table and Supplementary Figures S1-S7 from Pomalidomide Alters Pancreatic Macrophage Populations to Generate an Immune-Responsive Environment at Precancerous and Cancerous Lesions

Author

Peter Storz, Han W. Tun, John A. Copland, Brandy Edenfield, Yushi Qiu, Zhimin Li, Heike Doeppler, Christina A. von Roemeling, Alicia K. Fleming, Veethika Pandey, Geou-Yarh Liou, and Ligia I. Bastea

Abstract

Supplementary Table 1: Table with antibodies and dilutions used Supplementary Figure S1: Treatment scheme and analyses of stroma Supplementary Figure S2: Additional analyses of cell death and cell proliferation Supplementary Figure S3: Presence of Ym1+ macrophage and IL-13 in PanIN areas Supplementary Figure S4: Additional data on the role of IRF4 in macrophage polarization Supplementary Figure S5: Presence of macrophage-secreted factors and T cells Supplementary Figure S6: Treatment scheme and analyses of presence of immune cells Supplementary Figure S7: Blood counts and coagulation profile

Published
2023

5. Ym1

Author

Alicia K, Fleming Martinez, Heike R, Döppler, Ligia I, Bastea, Brandy H, Edenfield, Geou-Yarh, Liou, and Peter, Storz

Abstract

Desmoplasia around pancreatic lesions is a barrier for immune cells and a hallmark of developing and established pancreatic cancer. However, the contribution of the innate immune system to this process is ill-defined. Using the KC mouse model and primary cells

Published
2021

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