Immune Cell Modulation of the Extracellular Matrix Contributes to the Pathogenesis of Pancreatic Cancer

Ahmad, Ramiz S; Eubank, Timothy D.; Łukomski, Sławomir; Boone, Brian A.

doi:10.3390/biom11060901

Cited by 22 publications

(16 citation statements)

References 200 publications

(225 reference statements)

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“…One key functional biomarker of TAM polarization is MHC-II. 56 Among the roles ascribed to MHC-II– Mac within the TME are immunosuppression, 57,58 lymph/angiogenesis 59 , ECM deposition 60,61 and metastasis. 62 Here, we report a clear difference between the interaction rates of MHC-II+ and MHC-II-Mac populations with each EVs fraction.…”

Section: Discussionmentioning

confidence: 99%

Cancer stem cell-derived extracellular vesicles preferentially target MHC-II– macrophages and PD1+ T cells in the tumor microenvironment

González-Callejo

Guo

Ziglari

et al. 2022

Preprint

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Immunotherapy is an approved treatment option for head and neck squamous cell carcinoma (HNSCC). However, the response rate to immune checkpoint blockade is only 13% for recurrent HNSCC, highlighting the urgent need to better understand tumor-immune interplay, with the ultimate goal of improving patient outcomes. HNSCC present high local recurrence rates and therapy resistance that can be attributed to the presence of cancer stem cells (CSC) within tumors. CSC exhibit singular properties that enable them to avoid immune detection and eradication. The immune cell types that directly engage with CSC to allow immune escape and cancer recurrence are still unknown. Here, we genetically engineered CSC-derived extracellular vesicles (EVs) to perform sortase-mediated in vivo proximity labeling. We identified specific immune cell subsets recruited into the CSC niche. We demonstrated that unmanipulated CSC-EVs preferentially target MHC-II– macrophages and PD1+ T cells, and that such EV-mediated intercellular communication between CSC and these immune cells contributed to the observed spatial interactions and niche sharing. These results suggest that combination therapies targeting CSC, tumor macrophages and PD1 may synergize and lower local recurrence rates in HNSCC patients.

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Section: Discussionmentioning

confidence: 99%

Cancer stem cell-derived extracellular vesicles preferentially target MHC-II– macrophages and PD1+ T cells in the tumor microenvironment

González-Callejo

Guo

Ziglari

et al. 2022

Preprint

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“…Indeed, the stroma's mechanical properties, e.g., stiffness, are directly correlated to the pathogenesis of cancer. Ahmad et al note that the PDAC is characterized by a dense, fibrotic stroma composed of ECM proteins that poses a significant physical barrier that is immunosuppressive and obstructs penetration of cytotoxic chemotherapy agents into the tumor microenvironment (TME) [8]. These authors discuss the significant contribution of fibrosis to the pathogenesis of pancreatic cancer, with a focus on the crosstalk between immune cells and pancreatic stellate cells that contribute to ECM deposition.…”

Section: Ecm Effectors As Diagnostic Tools and Targetmentioning

confidence: 99%

Preface of the Special Issue on the Role of Extracellular Matrix in Development and Cancer Progression

Tzanakakis

Nikitovic

2022

Biomolecules

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“…Pancreatic cancer (PDAC) is another tumor with well-established links to fibrosis [ 145 ] ( Table 2 ). High expression of LOX is associated with a significantly shorter progression-free survival (PFS) [ 131 ] and poor response to chemotherapy [ 128 , 129 ].…”

Section: Altered Expression Of Lysyl Oxidases In Cancerous Settingsmentioning

confidence: 99%

Fibrosis in Mesothelioma: Potential Role of Lysyl Oxidases

Perryman

Gray

2022

Cancers

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Immunotherapies (such as checkpoint inhibitors) and standard chemotherapies (such as cisplatin) have limitations in the successful treatment of malignant pleural mesothelioma (MPM). Fibrosis is the accumulation of collagen in the extracellular matrix (ECM) of tissues, making them denser than that of healthy tissues and thereby affecting drug delivery and immune cell infiltration. Moreover, fibrosis severely affects the patient’s breathing and quality of life. The production of collagen and its assembly is highly regulated by various enzymes such as lysyl oxidases. Many solid tumors aberrantly express the family of lysyl oxidases (LOX/LOXL). This review examines how LOX/LOXLs were found to be dysregulated in noncancerous and cancerous settings, discusses their roles in solid tumor fibrosis and pathogenesis and explores the role of fibrosis in the development and poor clinical outcomes of patients with MPM. We examine the current preclinical status of drugs targeting LOX/LOXLs and how the incorporation of such drugs may have therapeutic benefits in the treatment and management of patients with MPM.

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Immune Cell Modulation of the Extracellular Matrix Contributes to the Pathogenesis of Pancreatic Cancer

Cited by 22 publications

References 200 publications

Cancer stem cell-derived extracellular vesicles preferentially target MHC-II– macrophages and PD1+ T cells in the tumor microenvironment

Cancer stem cell-derived extracellular vesicles preferentially target MHC-II– macrophages and PD1+ T cells in the tumor microenvironment

Preface of the Special Issue on the Role of Extracellular Matrix in Development and Cancer Progression

Fibrosis in Mesothelioma: Potential Role of Lysyl Oxidases

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