The Liver Pre-Metastatic Niche in Pancreatic Cancer: A Potential Opportunity for Intervention

Gumberger, Peter; Björnsson, Bergþór; Sandström, Per; Bojmar, Linda; Zambirinis, Constantinos P.

doi:10.3390/cancers14123028

Cited by 13 publications

(11 citation statements)

References 118 publications

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“…The recruitment of BMDCs in the liver can alter the phenotype of LSECs, HSCs, and immune cells. A PMN dominated by activated HSCs, metastasis-associated macrophages (MAMs), cancer-associated fibroblasts (CAFs), and various prometastatic factors is an optimal site for TC metastasis [81]. Among them, myeloid-derived suppressor cells (MDSC) is one of the most influential cell populations in BMDC, and it is closely related to the metastatic progression.…”

Section: The Formation Of Pmn In Liver and Its Relationship With Tumo...mentioning

confidence: 99%

Role of T cells in liver metastasis

Wu,

Zhang,

Shen

et al. 2024

Cell Death Dis

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The liver is a major metastatic site (organ) for gastrointestinal cancers (such as colorectal, gastric, and pancreatic cancers) as well as non-gastrointestinal cancers (such as lung, breast, and melanoma cancers). Due to the innate anatomical position of the liver, the apoptosis of T cells in the liver, the unique metabolic regulation of hepatocytes and other potential mechanisms, the liver tends to form an immunosuppressive microenvironment and subsequently form a pre-metastatic niche (PMN), which can promote metastasis and colonization by various tumor cells(TCs). As a result, the critical role of immunoresponse in liver based metastasis has become increasingly appreciated. T cells, a centrally important member of adaptive immune response, play a significant role in liver based metastases and clarifying the different roles of the various T cells subsets is important to guide future clinical treatment. In this review, we first introduce the predisposing factors and related mechanisms of liver metastasis (LM) before introducing the PMN and its transition to LM. Finally, we detail the role of different subsets of T cells in LM and advances in the management of LM in order to identify potential therapeutic targets for patients with LM.

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Section: The Formation Of Pmn In Liver and Its Relationship With Tumo...mentioning

confidence: 99%

Role of T cells in liver metastasis

Wu,

Zhang,

Shen

et al. 2024

Cell Death Dis

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“…MDSCs, CAFs and neutrophils contribute to the formation of the pre-metastatic niche by “priming” it [ 44 ]. Neutrophils or PMN-MDSCs are recruited to the pre-metastatic niches mostly through the chemokine receptors CXCR2 and CXCR4.…”

Section: The Tumor Microenvironmentmentioning

confidence: 99%

“…This leads to increased metastatic potential, to inhibition of NK cells and to increased extravasation. NETs finally trap tumor cells into the microvasculature [ 44 ].…”

Section: The Tumor Microenvironmentmentioning

confidence: 99%

Counteracting Immunosuppression in the Tumor Microenvironment by Oncolytic Newcastle Disease Virus and Cellular Immunotherapy

Schirrmacher¹,

Gool²,

Stuecker³

2022

IJMS

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An apparent paradox exists between the evidence for spontaneous systemic T cell- mediated anti-tumor immune responses in cancer patients, observed particularly in their bone marrow, and local tumor growth in the periphery. This phenomenon, known as “concomitant immunity” suggests that the local tumor and its tumor microenvironment (TME) prevent systemic antitumor immunity to become effective. Oncolytic Newcastle disease virus (NDV), an agent with inherent anti-neoplastic and immune stimulatory properties, is capable of breaking therapy resistance and immunosuppression. This review updates latest information about immunosuppression by the TME and discusses mechanisms of how oncolytic viruses, in particular NDV, and cellular immunotherapy can counteract the immunosuppressive effect of the TME. With regard to cellular immunotherapy, the review presents pre-clinical studies of post-operative active-specific immunotherapy and of adoptive T cell-mediated therapy in immunocompetent mice. Memory T cell (MTC) transfer in tumor challenged T cell-deficient nu/nu mice demonstrates longevity and functionality of these cells. Graft-versus-leukemia (GvL) studies in mice demonstrate complete remission of late-stage disease including metastases and cachexia. T cell based immunotherapy studies with human cells in human tumor xenotransplanted NOD/SCID mice demonstrate superiority of bone marrow-derived as compared to blood-derived MTCs. Results from clinical studies presented include vaccination studies using two different types of NDV-modified cancer vaccine and a pilot adoptive T-cell mediated therapy study using re-activated bone marrow-derived cancer-reactive MTCs. As an example for what can be expected from clinical immunotherapy against tumors with an immunosuppressive TME, results from vaccination studies are presented from the aggressive brain tumor glioblastoma multiforme. The last decades of basic research in virology, oncology and immunology can be considered as a success story. Based on discoveries of these research areas, translational research and clinical studies have changed the way of treatment of cancer by introducing and including immunotherapy.

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“…PDAC-derived metastases are detected in up to 50% of patients at the time of first diagnosis, with a remarkable predilection for the liver [ 72 ]. This process was recently studied in detail, showing that PDAC-derived exosomes promote the formation of a fibrotic environment in the liver and thus establish a pre-metastatic niche.…”

Section: The Complement System In Tumorigenic Processes Of Pdacmentioning

confidence: 99%

Complement and Fungal Dysbiosis as Prognostic Markers and Potential Targets in PDAC Treatment

et al. 2022

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Pancreatic ductal adenocarcinoma (PDAC) is still hampered by a dismal prognosis. A better understanding of the tumor microenvironment within the pancreas and of the factors affecting its composition is of utmost importance for developing new diagnostic and treatment tools. In this context, the complement system plays a prominent role. Not only has it been shown to shape a T cell-mediated immune response, but it also directly affects proliferation and apoptosis of the tumor cells, influencing angiogenesis, metastatic spread and therapeutic resistance. This makes complement proteins appealing not only as early biomarkers of PDAC development, but also as therapeutic targets. Fungal dysbiosis is currently the new kid on the block in tumorigenesis with cancer-associated mycobiomes extracted from several cancer types. For PDAC, colonization with the yeast Malassezia seems to promote cancer progression, already in precursor lesions. One responsible mechanism appears to be complement activation via the lectin pathway. In the present article, we review the role of the complement system in tumorigenesis, presenting observations that propose it as the missing link between fungal dysbiosis and PDAC development. We also present the results of a small pilot study supporting the crucial interplay between the complement system and Malassezia colonization in PDAC pathogenesis.

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The Liver Pre-Metastatic Niche in Pancreatic Cancer: A Potential Opportunity for Intervention

Cited by 13 publications

References 118 publications

Role of T cells in liver metastasis

Role of T cells in liver metastasis

Counteracting Immunosuppression in the Tumor Microenvironment by Oncolytic Newcastle Disease Virus and Cellular Immunotherapy

Complement and Fungal Dysbiosis as Prognostic Markers and Potential Targets in PDAC Treatment

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