State-of-the-art of regulatory dendritic cells in cancer

Conejo-Garcia, José R.; Rutkowski, Melanie R.; Cubillos-Ruiz, Juan R.

doi:10.1016/j.pharmthera.2016.04.003

Cited by 47 publications

(25 citation statements)

References 73 publications

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“…Ovarian cancer is a highly aggressive and lethal malignancy that subverts the normal function of host DCs as a key mechanism to suppress the development of protective immune responses (Conejo-Garcia et al, 2016; Scarlett et al, 2012). We postulated that hostile conditions within the tumor itself could trigger ER stress not only in cancer cells, but also in immune cells that reside in the same adverse milieu.…”

Section: Er Stress Responses In Tumor-associated Immune Cellsmentioning

confidence: 99%

Tumorigenic and Immunosuppressive Effects of Endoplasmic Reticulum Stress in Cancer

Cubillos-Ruiz

Bettigole²,

Glimcher

2017

Cell

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658

566

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SUMMARY Malignant cells utilize diverse strategies that enable them to thrive under adverse conditions while simultaneously inhibiting the development of anti-tumor immune responses. Hostile microenvironmental conditions within tumor masses, such as nutrient deprivation, oxygen limitation, high metabolic demand and oxidative stress disturb the protein folding capacity of the Endoplasmic Reticulum (ER), thereby provoking a cellular state of “ER stress”. Sustained activation of ER stress sensors endows malignant cells with greater tumorigenic, metastatic and drug resistant capacity. Additionally, recent studies have uncovered that ER stress responses further impede the development of protective anti-cancer immunity by manipulating the function of myeloid cells in the tumor microenvironment. Here, we discuss the tumorigenic and immunoregulatory effects of ER stress in cancer, and we explore the concept of targeting ER stress responses to enhance the efficacy of standard chemotherapies and evolving cancer immunotherapies in the clinic.

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Section: Er Stress Responses In Tumor-associated Immune Cellsmentioning

confidence: 99%

Tumorigenic and Immunosuppressive Effects of Endoplasmic Reticulum Stress in Cancer

Cubillos-Ruiz

Bettigole²,

Glimcher

2017

Cell

Self Cite

658

566

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“…However, tumor-associated cDCs or regulatory DC (regDCs) in the TME display altered functions with impaired cross-presentation capacity, express low levels of co-stimulatory molecules, and have high-proangiogenic abilities. These changes depend on diverse conditions that are established during tumor progression, for example, hypoxia, production of PGE2, IL-10, adenosine, and increased levels of lactate ( 117 – 119 ).…”

Section: Immature Myeloid Cells (Mdsc and Dc)mentioning

confidence: 99%

Contribution to Tumor Angiogenesis From Innate Immune Cells Within the Tumor Microenvironment: Implications for Immunotherapy

et al. 2018

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The critical role of angiogenesis in promoting tumor growth and metastasis is strongly established. However, tumors show considerable variation in angiogenic characteristics and in their sensitivity to antiangiogenic therapy. Tumor angiogenesis involves not only cancer cells but also various tumor-associated leukocytes (TALs) and stromal cells. TALs produce chemokines, cytokines, proteases, structural proteins, and microvescicles. Vascular endothelial growth factor (VEGF) and inflammatory chemokines are not only major proangiogenic factors but are also immune modulators, which increase angiogenesis and lead to immune suppression. In our review, we discuss the regulation of angiogenesis by innate immune cells in the tumor microenvironment, specific features, and roles of major players: macrophages, neutrophils, myeloid-derived suppressor and dendritic cells, mast cells, γδT cells, innate lymphoid cells, and natural killer cells. Anti-VEGF or anti-inflammatory drugs could balance an immunosuppressive microenvironment to an immune permissive one. Anti-VEGF as well as anti-inflammatory drugs could therefore represent partners for combinations with immune checkpoint inhibitors, enhancing the effects of immune therapy.

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“…DCs have been long considered as a critical component of antitumor immunity, in particular, by their capacity to cross-present self-tumor antigens to CD8 + T cells. However, in the tumor context, DCs can be severely limited in their differentiation and activation and are poor stimulators of immune responses [108,109]. Among the mechanisms of negative regulation of DC functions, hypoxia, which characterizes the tumor microenvironment, impairs DC maturation and induces their transcriptional reprogramming [46,110].…”

Section: Dc-derived Opn In Tumor Progressionmentioning

confidence: 99%

Role of osteopontin in dendritic cell shaping of immune responses

Prete

Scutera

Sozzani

et al. 2019

Cytokine & Growth Factor Reviews

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Osteopontin (OPN) is a pleiotropic cytokine produced both by immune and non-immune cells and active on different cellular targets. OPN production has been associated with several pathological conditions, including autoimmune diseases (e.g. lupus, multiple sclerosis and rheumatoid arthritis) and cancer. Emerging evidence suggests that the role of OPN has been underestimated, as it seems to be working at multiple levels of immune regulation, such as the shaping of T cell effector responses, the regulation of the tumor microenvironment, and the functional interaction with mesenchymal stromal cells. In this context, dendritic cells (DCs) play a crucial role being both an important source and a cellular target for OPN action. DC family is composed by several cell subsets endowed with specific immune functions. OPN exerts its biological functions through multiple receptors and is produced in different intracellular and secreted forms. OPN production by DC subsets is emerging as a crucial mechanism of regulation in normal and pathological conditions and starts to be exploited as a therapeutic target. This review will focus on the role of DC-derived OPN in shaping immune response and on the complex role of this cytokines in the regulation in immune response.

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State-of-the-art of regulatory dendritic cells in cancer

Cited by 47 publications

References 73 publications

Tumorigenic and Immunosuppressive Effects of Endoplasmic Reticulum Stress in Cancer

Tumorigenic and Immunosuppressive Effects of Endoplasmic Reticulum Stress in Cancer

Contribution to Tumor Angiogenesis From Innate Immune Cells Within the Tumor Microenvironment: Implications for Immunotherapy

Role of osteopontin in dendritic cell shaping of immune responses

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