Dendritic cells in the tumor microenvironment: prognostic and theranostic impact

Verneau, Johanna; Sautès-Fridman, Catheriné; Sun, Chengming

doi:10.1016/j.smim.2020.101410

Cited by 102 publications

(80 citation statements)

References 140 publications

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“…In this context, DCs can be viewed as promising targets for cancer immunotherapy. Indeed, increased DC density, mostly of cDCs, within the TME is associated with better prognosis in ovarian carcinoma, lung cancers, and breast cancers (103)(104)(105). However, the TME can elicit multiple mechanisms to perturb DC functions, including decreased production of chemoattractants (e.g., CCL4 and CCL5), which impairs the recruitment of DCs to the tumor bed, and a reduction in survival signals [such as the growth factor FMS-like tyrosine kinase 3 ligand (FLT3L)] required for DC differentiation and viability (106).…”

Section: Dcsmentioning

confidence: 99%

Therapeutic Targeting of the Tumor Microenvironment

2021

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The importance of the tumor microenvironment (TME) in dynamically regulating cancer progression and influencing therapeutic outcome is now widely appreciated, and multiple therapies directed to various components of the TME have been developed in recent years. In this review, we will introduce the key cell types and features of the TME; discuss how these can be therapeutically targeted, with an emphasis on therapies that are under clinical evaluation or have been approved; highlight how the TME is altered by various interventions including standardof-care therapies; and conclude with an overview of the opportunities and potential challenges to consider in the coming years.The TME is defined as the complex and rich multicellular environment in which a tumor develops. The TME typically comprises immune cells, including T and B lymphocytes, tumor-associated macrophages (TAM), dendritic cells (DC), natural killer (NK) cells, neutrophils, and myeloid-derived suppressor cells (MDSC); stromal cells such as cancer-associated fibroblasts (CAF), pericytes, and mesenchymal stromal cells; the extracellular matrix (ECM) and other secreted molecules, such as growth factors, cytokines, chemokines, and extracel-absTRaCT Strategies to therapeutically target the tumor microenvironment (TME) have emerged as a promising approach for cancer treatment in recent years due to the critical roles of the TME in regulating tumor progression and modulating response to standard-of-care therapies. Here, we summarize the current knowledge regarding the most advanced TME-directed therapies, which have either been clinically approved or are currently being evaluated in trials, including immunotherapies, antiangiogenic drugs, and treatments directed against cancer-associated fibroblasts and the extracellular matrix. We also discuss some of the challenges associated with TME therapies, and future perspectives in this evolving field.Significance: This review provides a comprehensive analysis of the current therapies targeting the TME, combining a discussion of the underlying basic biology with clinical evaluation of different therapeutic approaches, and highlighting the challenges and future perspectives.Research.

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Section: Dcsmentioning

confidence: 99%

Therapeutic Targeting of the Tumor Microenvironment

2021

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“…The heterogeneity of moDCs may explain the contradictory roles observed in many types of cancers. Notably, moDCs are primarily generated in response to inflammation and promote CD4 + T-cell differentiation towards a Th1, Th2 or Th17 cell phenotype [45]. They are also effective in cross-presenting tumor antigens towards CD8 + T cells and inducing their infiltration into the TME of different mouse tumor models [46].…”

Section: Modcsmentioning

confidence: 99%

“…cDC1 and cDC2 also locally induce IL-12 production and subsequently CD8 + T cell cytotoxicity and IFN-α/β production [60]. cDC2s produce a wide variety of cytokines important for CD4 + T-cell activation and Th1 and Th2 responses, such as IL-1β, IL-6, IL-12 and IL-23 [45].…”

Section: Chemokine Network and Dcs In The Tmementioning

confidence: 99%

Dendritic Cells: Behind the Scenes of T-Cell Infiltration into the Tumor Microenvironment

Lucarini

Tempora

D’Amico

et al. 2021

Cancers

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Tumor-infiltrating CD8+ T cells have been shown to play a crucial role in controlling tumor progression. However, the recruitment and activation of these immune cells at the tumor site are strictly dependent on several factors, including the presence of dendritic cells (DCs), the main orchestrators of the antitumor immune responses. Among the various DC subsets, the role of cDC1s has been demonstrated in several preclinical experimental mouse models. In addition, the high density of tumor-infiltrating cDC1s has been associated with improved survival in many cancer patients. The ability of cDC1s to modulate antitumor activity depends on their interaction with other immune populations, such as NK cells. This evidence has led to the development of new strategies aimed at increasing the abundance and activity of cDC1s in tumors, thus providing attractive new avenues to enhance antitumor immunity for both established and novel anticancer immunotherapies. In this review, we provide an overview of the various subsets of DCs, focusing in particular on the role of cDC1s, their ability to interact with other intratumoral immune cells, and their prognostic significance on solid tumors. Finally, we outline key therapeutic strategies that promote the immunogenic functions of DCs in cancer immunotherapy.

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“…In the TME, TAMs are mainly of the M2 phenotype, which promote tumor proliferation and metastasis ( 5 ). DC function to present antigens, and those in the TME usually exist in an immature state and promote tumor progression ( 6 ). In addition, MDSC and Treg can promote tumor progression by exerting immunosuppressive effects ( 7 ).…”

Section: Introductionmentioning

confidence: 99%

Tumor Immune Microenvironment and Its Related miRNAs in Tumor Progression

Xing

Ruan

et al. 2021

Front. Immunol.

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MiRNA is a type of small non-coding RNA, by regulating downstream gene expression that affects the progression of multiple diseases, especially cancer. MiRNA can participate in the biological processes of tumor, including proliferation, invasion and escape, and exhibit tumor enhancement or inhibition. The tumor immune microenvironment contains numerous immune cells. These cells include lymphocytes with tumor suppressor effects such as CD8+ T cells and natural killer cells, as well as some tumor-promoting cells with immunosuppressive functions, such as regulatory T cells and myeloid-derived suppressor cells. MiRNA can affect the tumor immune microenvironment by regulating the function of immune cells, which in turn modulates the progression of tumor cells. Investigating the role of miRNA in regulating the tumor immune microenvironment will help elucidate the specific mechanisms of interaction between immune cells and tumor cells, and may facilitate the use of miRNA as a predictor of immune disorders in tumor progression. This review summarizes the multifarious roles of miRNA in tumor progression through regulation of the tumor immune microenvironment, and provides guidance for the development of miRNA drugs to treat tumors and for the use of miRNA as an auxiliary means in tumor immunotherapy.

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Dendritic cells in the tumor microenvironment: prognostic and theranostic impact

Cited by 102 publications

References 140 publications

Therapeutic Targeting of the Tumor Microenvironment

Therapeutic Targeting of the Tumor Microenvironment

Dendritic Cells: Behind the Scenes of T-Cell Infiltration into the Tumor Microenvironment

Tumor Immune Microenvironment and Its Related miRNAs in Tumor Progression

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