Type 1 conventional dendritic cells: ontogeny, function, and emerging roles in cancer immunotherapy

Zhang, Shengbo; Chopin, Michaël; Nutt, Stephen L.

doi:10.1016/j.it.2021.10.004

Cited by 20 publications

(17 citation statements)

References 133 publications

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“…Many recent scRNA-seq studies provide us with a deep understanding of the heterogeneity of DC states in human cancer, and a meta-analysis of such data across human lung, breast, liver, colorectal, and ovarian tumors has defined cDC1, cDC2, DC3, pDC, and cDC2/MoDC cell subsets and their transcriptional signatures ( 154 ). Of these, cDC1 cells in particular are considered critical for the priming of CD8 T cells and for effective induction of antitumor immunity ( 155 ). Less is however known about how tumors affect systemic DC development.…”

Section: Development Of Other Immune and Hematopoietic Cell Lineages ...mentioning

confidence: 99%

Hematologic dysfunction in cancer: Mechanisms, effects on antitumor immunity, and roles in disease progression

2022

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With the major advances in cancer immunology and immunotherapy, it is critical to consider that most immune cells are short-lived and need to be continuously replenished from hematopoietic stem and progenitor cells. Hematologic abnormalities are prevalent in cancer patients, and many ground-breaking studies over the past decade provide insights into their underlying cellular and molecular mechanisms. Such studies demonstrate that the dysfunction of hematopoiesis is more than a side-effect of cancer pathology, but an important systemic feature of cancer disease. Here we review these many advances, covering the cancer-associated phenotypes of hematopoietic stem and progenitor cells, the dysfunction of myelopoiesis and erythropoiesis, the importance of extramedullary hematopoiesis in cancer disease, and the developmental origins of tumor associated macrophages. We address the roles of many secreted mediators, signaling pathways, and transcriptional and epigenetic mechanisms that mediate such hematopoietic dysfunction. Furthermore, we discuss the important contribution of the hematopoietic dysfunction to cancer immunosuppression, the possible avenues for therapeutic intervention, and highlight the unanswered questions and directions for future work. Overall, hematopoietic dysfunction is established as an active component of the cancer disease mechanisms and an important target for therapeutic intervention.

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Section: Development Of Other Immune and Hematopoietic Cell Lineages ...mentioning

confidence: 99%

Hematologic dysfunction in cancer: Mechanisms, effects on antitumor immunity, and roles in disease progression

2022

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“…However, to date, various challenges limit their effectiveness in treatments. For instance, DCs need to be mature and able to migrate to the tumour 22 . Despite a lot of interest for the role of chemokines in the migration of DCs 3 , few studies have explored their mechanical properties, even if evidence suggests that they are closely linked to their migration potential and function 5 , 23 .…”

Section: Discussionmentioning

confidence: 99%

Immature and mature bone marrow-derived dendritic cells exhibit distinct intracellular mechanical properties

Leblanc-Hotte

Audiger

Chabot‐Roy

et al. 2023

Sci Rep

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Dendritic cells (DCs) patrol the organism at an immature stage to detect the presence of pathogens. Once activated, these mature DCs reach the lymph nodes to activate antigen-specific T lymphocytes and thus initiate an adaptative immune response to control the pathogen. The migration of both immature and mature DCs is a key process for their optimal function. DC migration requires transit through narrow constrictions that is allowed by their high local and global deformation capabilities. In addition to cytoplasmic changes, the nucleus mechanical properties also have a major impact for cellular migration and motility. Yet, nucleus intracellular mobility of dendritic cells or its variation upon maturation have not been investigated. Our study defines the biophysical phenotypic variations of dendritic cells upon maturation using interferometric deformability cytometry. This method characterizes different cellular mechanical properties, such as elongation and nucleus offset, by assessing the refractive index spatial distribution of shear-induced deformed cells. By using these parameters, our data suggest that in vitro bone marrow derived dendritic cell (BMDC) maturation induces cell stiffening and reduces nucleus mobility, allowing to distinguish immature and mature dendritic cells. Overall, our method provides insights on intracellular mechanical properties of two dendritic cell states.

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“…These results indicated that Zeb1-de cient cDC1s from the liver might have an impaired capability of cross presentation. Accumulating evidence has established that cDC1s are particularly adept at uptake of dead tumor cells and at cross-priming tumor-speci c CD8 + T cells within tumor microenvironment or after migration to tumor draining lymph nodes (tumor dLNs) 41,42 . To examine the role of Zeb1 in the function of cDC1s, we challenged WT and Zeb1-dcKO mice subcutaneously with 2×10 5 B16F10 melanoma cells.…”

Section: Ablation Of Zeb1 In Dcs Dampens Antitumor Immunitymentioning

confidence: 99%

The transcription factor Zeb1 controls homeostasis and function of type 1 conventional dendritic cells

Wang

zhang

et al. 2023

Preprint

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Type 1 conventional dendritic cells (cDC1s) are the most efficient cross-presenting cells that induce protective cytotoxic T cell response. However, the regulation of their homeostasis and function is incompletely understood. Here we observed a selective reduction of splenic cDC1s in mice with Zeb1 deficiency in dendritic cells, due to excessive cell death, rendering mice higher resistance to Listeria infection. Moreover, cDC1s from other sources of Zeb1-deficient mice displayed impaired cross-presentation of exogenous antigens, resulting in compromised antitumor CD8+ T cell responses. Mechanistically, Zeb1 facilitated the production of phagosomal reactive oxygen species by repressing the expression of microRNA-96 that targeted Cybb mRNA of NADPH oxidase Nox2. Consequently, loss of Zeb1 in cDC1s diminished phagosomal membrane rupture that permits antigen export to the cytosol. Cybb re-expression in Zeb1-deficient cDC1s fully restored the defective cross-presentation while microRNA-96 overexpression in Zeb1-sufficient cDC1s inhibited cross-presentation. Therefore, our results identify a novel Zeb1-microRNA-96-Cybb pathway that controls cross-presentation in cDC1s and uncover an essential role of Zeb1in cDC1 homeostasis.

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Type 1 conventional dendritic cells: ontogeny, function, and emerging roles in cancer immunotherapy

Cited by 20 publications

References 133 publications

Hematologic dysfunction in cancer: Mechanisms, effects on antitumor immunity, and roles in disease progression

Hematologic dysfunction in cancer: Mechanisms, effects on antitumor immunity, and roles in disease progression

Immature and mature bone marrow-derived dendritic cells exhibit distinct intracellular mechanical properties

The transcription factor Zeb1 controls homeostasis and function of type 1 conventional dendritic cells

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