Functional Role of Dendritic Cell Subsets in Cancer Progression and Clinical Implications

Prete, Annalisa Del; Sozio, Francesca; Barbazza, Ilaria; Salvi, Valentina; Tiberio, Laura; Laffranchi, Mattia; Gismondi, Angela; Bosisio, Daniela; Schioppa, Tiziana; Sozzani, Silvano

doi:10.3390/ijms21113930

Cited by 62 publications

(87 citation statements)

References 209 publications

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“…The inhibition of DCs’ viability by TME is not restricted to the hypoxic microenvironment. Tumor-derived factors, such as VEGF-A, PGE2, and ATP, keep infiltrating DCs at an immature state that is not functional for the activation of T cell response [ 10 ]. Indeed, one of the characteristics of the TME is the accumulation of immature DCs that are not able to finally differentiate.…”

Section: Discussionmentioning

confidence: 99%

“…In this context, tumors impair DC biology in many ways, including the modulation of DC differentiation, and the modification of their metabolism by decreasing the availability of nutrients and oxygen, and, therefore, by compromising DC viability [ 3 ]. Previous reports have shown that DCs are affected by hypoxia in terms of cell survival, differentiation, activation, and migration [ 9 , 10 ]. In addition, we have previously demonstrated that a prolonged exposure to hypoxia resulted in a pro-apoptotic program in immature DCs, along with PI3K/AKT inhibition [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

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Hypoxia Enhances the Expression of RNASET2 in Human Monocyte-Derived Dendritic Cells: Role of PI3K/AKT Pathway

Monaci

Coppola

Giuntini

et al. 2021

IJMS

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Hypoxia is a key component of the tumor microenvironment (TME) and promotes not only tumor growth and metastasis, but also negatively affects infiltrating immune cells by impairing host immunity. Dendritic cells (DCs) are the most potent antigen-presenting cells and their biology is weakened in the TME in many ways, including the modulation of their viability. RNASET2 belongs to the T2 family of extracellular ribonucleases and, besides its nuclease activity, it exerts many additional functions. Indeed, RNASET2 is involved in several human pathologies, including cancer, and it is functionally relevant in the TME. RNASET2 functions are not restricted to cancer cells and its expression could be relevant also in other cell types which are important players in the TME, including DCs. Therefore, this study aimed to unravel the effect of hypoxia (2% O2) on the expression of RNASET2 in DCs. Here, we showed that hypoxia enhanced the expression and secretion of RNASET2 in human monocyte-derived DCs. This paralleled the HIF-1α accumulation and HIF-dependent and -independent signaling, which are associated with DCs’ survival/autophagy/apoptosis. RNASET2 expression, under hypoxia, was regulated by the PI3K/AKT pathway and was almost completely abolished by TLR4 ligand, LPS. Taken together, these results highlight how hypoxia- dependent and -independent pathways shape RNASET2 expression in DCs, with new perspectives on its implication for TME and, therefore, in anti-tumor immunity.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Hypoxia Enhances the Expression of RNASET2 in Human Monocyte-Derived Dendritic Cells: Role of PI3K/AKT Pathway

Monaci

Coppola

Giuntini

et al. 2021

IJMS

Self Cite

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“…Due to the prominent biological features of DCs that are associated with initiation of the adaptive immune response, DCs are no doubt an ideal vaccine target to prevent cancers. Moreover, DCs secrete various kinds of cytokines and chemokines, which are indispensable for T cell proliferation, activation, and recruitment [138,139]. Thus, numerous preclinical and clinical trials have been initiated in previous decades to assess DC-based mRNA vaccines.…”

Section: Dendritic-cell-based Mrna Vaccinesmentioning

confidence: 99%

mRNA-Based Cancer Vaccines: A Therapeutic Strategy for the Treatment of Melanoma Patients

et al. 2021

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Malignant melanoma is one of the most aggressive forms of cancer and the leading cause of death from skin tumors. Given the increased incidence of melanoma diagnoses in recent years, it is essential to develop effective treatments to control this disease. In this regard, the use of cancer vaccines to enhance cell-mediated immunity is considered to be one of the most modern immunotherapy options for cancer treatment. The most recent cancer vaccine options are mRNA vaccines, with a focus on their usage as modern treatments. Advantages of mRNA cancer vaccines include their rapid production and low manufacturing costs. mRNA-based vaccines are also able to induce both humoral and cellular immune responses. In addition to the many advantages of mRNA vaccines for the treatment of cancer, their use is associated with a number of challenges. For this reason, before mRNA vaccines can be used for the treatment of cancer, comprehensive information about them is required and a large number of trials need to be conducted. Here, we reviewed the general features of mRNA vaccines, including their basis, stabilization, and delivery methods. We also covered clinical trials involving the use of mRNA vaccines in melanoma cancer and the challenges involved with this type of treatment. This review also emphasized the combination of treatment with mRNA vaccines with the use of immune-checkpoint blockers to enhance cell-mediated immunity.

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“…The TME is home to several soluble factors that may promote a tolerogenic or immunosuppressive DC phenotype; these include IL-10, IL-6, VEGF, CSF-1, β-catenin, TGF-β and PGE2 [ 62 ]. VEGF [ 63 ], β-catenin [ 64 ] and PGE2 [ 65 , 66 ] production by tumour cells and IL-10 secretion by tumour-associated macrophages [ 67 ] have been shown to inhibit DC function and/or recruitment.…”

Section: Cell Typesmentioning

confidence: 99%

Directing the Future Breakthroughs in Immunotherapy: The Importance of a Holistic Approach to the Tumour Microenvironment

Newnes

Armitage

Audsley

et al. 2021

Cancers

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Immunotherapy has revolutionised the treatment of cancers by exploiting the immune system to eliminate tumour cells. Despite the impressive response in a proportion of patients, clinical benefit has been limited thus far. A significant focus to date has been the identification of specific markers associated with response to immunotherapy. Unfortunately, the heterogeneity between patients and cancer types means identifying markers of response to therapy is inherently complex. There is a growing appreciation for the role of the tumour microenvironment (TME) in directing response to immunotherapy. The TME is highly heterogeneous and contains immune, stromal, vascular and tumour cells that all communicate and interact with one another to form solid tumours. This review analyses major cell populations present within the TME with a focus on their diverse and often contradictory roles in cancer and how this informs our understanding of immunotherapy. Furthermore, we discuss the role of integrated omics in providing a comprehensive view of the TME and demonstrate the potential of leveraging multi-omics to decipher the underlying mechanisms of anti-tumour immunity for the development of novel immunotherapeutic strategies.

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Functional Role of Dendritic Cell Subsets in Cancer Progression and Clinical Implications

Cited by 62 publications

References 209 publications

Hypoxia Enhances the Expression of RNASET2 in Human Monocyte-Derived Dendritic Cells: Role of PI3K/AKT Pathway

Hypoxia Enhances the Expression of RNASET2 in Human Monocyte-Derived Dendritic Cells: Role of PI3K/AKT Pathway

mRNA-Based Cancer Vaccines: A Therapeutic Strategy for the Treatment of Melanoma Patients

Directing the Future Breakthroughs in Immunotherapy: The Importance of a Holistic Approach to the Tumour Microenvironment

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