Neutrophils as Orchestrators in Tumor Development and Metastasis Formation

Kalafati, Lydia; Mitroulis, Ioannis; Verginis, Panayotis; Chavakis, Triantafyllos; Kourtzelis, Ioannis

doi:10.3389/fonc.2020.581457

Cited by 38 publications

(34 citation statements)

References 128 publications

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“…N2 neutrophils act via producing and releasing ROS and nitric oxide (NO), which increase DNA instability. Pro-tumor N2 TANs can inhibit T cell proliferation via expression of arginase 1 and induce T cell apoptosis via NO production [ 188 ]. N2 TANs could contribute to tumor invasion and angiogenesis through the production of MMP9 and VEGF in the primary and metastatic sites [ 12 ].…”

Section: Reviewmentioning

confidence: 99%

Systemic Interleukins’ Profile in Early and Advanced Colorectal Cancer

Czajka-Francuz

Cisoń-Jurek

Czajka

et al. 2021

IJMS

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Tumor microenvironment (TME) is characterized by mutual interactions of the tumor, stromal and immune cells. Early and advanced colorectal tumors differ in structure and present altered serum cytokine levels. Mutual crosstalk among TME infiltrating cells may shift the balance into immune suppressive or pro-inflammatory, antitumor response this way influencing patients’ prognosis. Cancer-related inflammation affects all the body and this way, the systemic level of cytokines could reflect TME processes. Despite numerous studies, it is still not known how systemic cytokines levels change during colorectal cancer (CRC) tumor development. Better understanding tumor microenvironment processes could help in planning therapeutic interventions and more accurate patient prognosis. To contribute to the comprehension of these processes within TME, we reviewed cytokines levels from clinical trials in early and advanced colorectal cancer. Presented data were analyzed in the context of experimental studies and studies analyzing tumor infiltration with immune cells. The review summarizes clinical data of cytokines secreted by tumor microenvironment cells: lymphocytes T helper 1 (Th1), lymphocytes T helper 2 (Th2), lymphocytes T helper 17 (Th17), regulatory T cells (Treg cells), regulatory T cells (Breg cells), M1/M2 macrophages, N1/N2 neutrophils, myeloid-derived suppressor cells (MDSC), dendritic cells (DC), innate lymphoid cells (ILC) natural killer (NK) cells and tumor cells.

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Section: Reviewmentioning

confidence: 99%

Systemic Interleukins’ Profile in Early and Advanced Colorectal Cancer

Czajka-Francuz

Cisoń-Jurek

Czajka

et al. 2021

IJMS

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“…The N1 TANs, activated by type I IFNs, inhibit angiogenesis and effectively eliminate tumor cells via antibody dependent cell-mediated cytotoxicity (ADCC) and phagocytosis. On the other hand, N2 TANs inhibit T-cell proliferation (ARG-1 activity) and induce T-cell apoptosis (NO production) [ 66 , 67 ]. TANs contribute also to the tumor invasion and angiogenesis through the production of MMP9 and vascular endothelial growth factor (VEGF) in the primary and metastatic sites [ 51 ].…”

Section: Tumor-infiltrating Neutrophils—a Double Edged Sword In Crmentioning

confidence: 99%

Granulocytes and Cells of Granulocyte Origin—The Relevant Players in Colorectal Cancer

Siemińska

Poljańska

Baran

2021

IJMS

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Colorectal cancer (CRC) is one of the most common malignancy and cause of cancer death worldwide, and it still remains a therapeutic challenge for western medicine. There is strong evidence that, in addition to genetic predispositions, environmental factors have also a substantial impact in CRC development. The risk of CRC is attributed, among others to dietary habits, alcohol consumption, whereas physical activity, food containing dietary fiber, dairy products, and calcium supplements have a protective effect. Despite progress in the available therapies, surgery remains a basic treatment option for CRC. Implementation of additional methods of treatment such as chemo- and/or targeted immunotherapy, improved survival rates, however, the results are still far from satisfactory. One of the reasons may be the lack of deeper understanding of the interactions between the tumor and different types of cells, including tumor infiltrating granulocytes. While the role of neutrophils is quite well explored in many cancers, role of eosinophils and basophils is often underestimated. As part of this review, we focused on the function of different granulocyte subsets in CRC, emphasizing the beneficial role of eosinophils and basophils, as well as dichotomic mode of neutrophils action. In addition, we addressed the current knowledge on cells of granulocyte origin, specifically granulocytic myeloid derived suppressor cells (Gr-MDSCs) and their role in development and progression of CRC.

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“…These changes are consistent with strong inflammation in the tumor caused by VSV-S infection. Neutrophils exhibit tumor suppressive activities by generating reactive oxygen species (ROS), activation of the IFN-γ pathway, and up-regulation of antigen presentation [42]. The large increase of neutrophils in tumors could cause more death of cancer cells due to innate immunity [43].…”

Section: Discussionmentioning

confidence: 99%

Modulation of the tumor microenvironment by armed vesicular stomatitis virus in a syngeneic pancreatic cancer model

Tang

Shi

Luker

et al. 2022

Virol J

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Background The immunosuppressive microenvironment in pancreatic ductal adenocarcinoma is a major factor that limits the benefits of immunotherapy, especially immune checkpoint blockade. One viable strategy for reverting the immunosuppressive conditions is the use of an oncolytic virus (OV) in combination with other immunotherapy approaches. Infection of PDAC cells with a robust OV can change the tumor microenvironment and increase tumor antigen release by its lytic activities. These changes in the tumor may improve responses to immunotherapy, including immune checkpoint blockade. However, a more potent OV may be required for efficiently infecting pancreatic tumors that may be resistant to OV. Methods Vesicular stomatitis virus, a rapid replicating OV, was armed to express the Smac protein during virus infection (VSV-S). Adaptation by limited dilution largely increased the selective infection of pancreatic cancer cells by VSV-S. The engineered OV was propagated to a large quantity and evaluated for their antitumor activities in an animal model. Results In a syngeneic KPC model, intratumoral injection of VSV-S inhibited tumor growth, and induced increasing tumor infiltration of neutrophils and elimination of myeloid derived suppressor cells and macrophages in the tumor. More importantly, M2-like macrophages were eliminated preferentially over those with an M1 phenotype. Reduced levels of arginase 1, TGF-β and IL-10 in the tumor also provided evidence for reversion of the immunosuppressive conditions by VSV-S infection. In several cases, tumors were completely cleared by VSV-S treatment, especially when combined with anti-PD-1 therapy. A long-term survival of 44% was achieved. Conclusions The improved OV, VSV-S, was shown to drastically alter the immune suppressive tumor microenvironment when intratumorally injected. Our results suggest that the combination of potent OV treatment with immune checkpoint blockade may be a promising strategy to treat pancreatic cancer more effectively.

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Neutrophils as Orchestrators in Tumor Development and Metastasis Formation

Cited by 38 publications

References 128 publications

Systemic Interleukins’ Profile in Early and Advanced Colorectal Cancer

Systemic Interleukins’ Profile in Early and Advanced Colorectal Cancer

Granulocytes and Cells of Granulocyte Origin—The Relevant Players in Colorectal Cancer

Modulation of the tumor microenvironment by armed vesicular stomatitis virus in a syngeneic pancreatic cancer model

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