Harnessing the beneficial heterologous effects of vaccination

Goodridge, Helen S.; Ahmed, S. Sohail; Curtis, Nigel; Kollmann, Tobias R.; Levy, Ofer; Netea, Mihai G.; Pollard, Andrew J.; Crevel, Reinout van; Wilson, Christopher

doi:10.1038/nri.2016.43

Cited by 222 publications

(187 citation statements)

References 101 publications

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“…Finally, recent studies have demonstrated that monocyte and macrophage function can be modified for extended periods following microbial exposure due to metabolic and epigenetic changes (“trained immunity” or “innate immune memory”), which can confer long-term, lymphocyte-independent protection against pathogens and may underlie some clinical observations of heterologous effects of vaccination, especially in infants (Goodridge et al, 2016). These effects are likely maintained by epigenetic modification of myeloid progenitors (and even HSCs), as well as long-lived tissue-resident macrophages.…”

Section: Discussionmentioning

confidence: 99%

Granulocyte-Monocyte Progenitors and Monocyte-Dendritic Cell Progenitors Independently Produce Functionally Distinct Monocytes

et al. 2017

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Summary Granulocyte-monocyte progenitors (GMPs) and monocyte-dendritic cell progenitors (MDPs) produce monocytes during homeostasis and in response to increased demand during infection. Both progenitor populations are thought to derive from common myeloid progenitors (CMPs), and a hierarchical relationship (CMP-GMP-MDP-monocyte) is presumed to underlie monocyte differentiation. Here, however, we demonstrate that mouse MDPs arose from CMPs independently of GMPs, and that GMPs and MDPs produced monocytes via similar, but distinct, monocyte-committed progenitors. GMPs and MDPs yielded classical (Ly6Chi) monocytes with gene expression signatures that were defined by their origins and impacted their function. GMPs produced a subset of “neutrophil-like” monocytes, whereas MDPs gave rise to a subset of monocytes that yielded monocyte-derived dendritic cells. GMPs and MDPs were also independently mobilized to produce specific combinations of myeloid cell types following the injection of microbial components. Thus, the balance of GMP and MDP differentiation shapes the myeloid cell repertoire during homeostasis and following infection.

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Section: Discussionmentioning

confidence: 99%

Granulocyte-Monocyte Progenitors and Monocyte-Dendritic Cell Progenitors Independently Produce Functionally Distinct Monocytes

et al. 2017

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“…To this end, monocytes and macrophages that are exposed to certain stimuli can develop metabolic and epigenetic changes that lead to long-term alterations in subsequent responses by these cells. To further highlight their versatility, the memory established in monocytes and macrophages can be stimulatory or suppressive, with both effects often occurring simultaneously, depending on which genes are expressed or suppressed [57]. The process of macrophage “priming” or “training” occurs when prior exposure to a specific stimulus induces an enhanced immune response, such as increased microbicidal activity (i.e., increased phagocytic activity and increased expression of pro-inflammatory genes) [58].…”

Section: Text Of the Reviewmentioning

confidence: 99%

Transfusion-related immunomodulation: a reappraisal

Youssef¹,

Spitalnik

2017

Current Opinion in Hematology

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Purpose of Review This review summarizes current and prior observations regarding transfusion-related immunomodulation (TRIM) and puts these ideas into a modern immunological context, incorporating concepts from innate, adaptive, and nutritional immunity. We propose that TRIM research focus on determining whether there are specific, well-defined immunosuppressive effects from transfusing “pure” red blood cells (RBCs) themselves, along with the by-products produced by the stored RBCs as a result of the “storage lesion.” Macrophages are a key cell type involved in physiological and pathological RBC clearance and iron recycling. The plasticity and diversity of macrophages makes these cells potential mediators of immune suppression that could constitute TRIM. Recent Findings Recent reports identified the capacity of macrophages and monocytes to exhibit “memory.” Exposure to various stimuli, such as engulfment of apoptotic cells and interactions with ß-glucan and lipopolysaccharide, were found to induce epigenetic, metabolic, and functional changes in certain myeloid cells, particularly macrophages and monocytes. Summary Macrophages may mediate the immunosuppressive aspects of TRIM that arise as a result of transfused RBCs and their storage lesion induced by-products.

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“…A large majority of these studies involve either short TAA-derived peptides that can directly bind to MHC Class I or II molecules expressed by antigen-presenting cells 176 (42 studies), or SLPs that are processed intracellularly and then loaded on MHC Class I or II molecules 172,177,178 (22 studies), most often in combination with immunological adjuvants 179-182 like montanide ISA-51 (water-in-oil emulsion) 181,183 Hiltonol® (poly- L -lysine in carboxymethylcellulose, a TLR3 ligand) 184 and GM-CSF. 183,185-187 In several instances, vaccination is further combined with standard treatment regimens including conventional chemotherapy, 117,188-191 radiation therapy, 52,192-195 and targeted anticancer agents, 196-199 or with various immunotherapeutic interventions.…”

Section: Ongoing Clinical Trialsmentioning

confidence: 99%

Trial watch: Peptide-based vaccines in anticancer therapy

et al. 2018

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Peptide-based anticancer vaccination aims at stimulating an immune response against one or multiple tumor-associated antigens (TAAs) following immunization with purified, recombinant or synthetically engineered epitopes. Despite high expectations, the peptide-based vaccines that have been explored in the clinic so far had limited therapeutic activity, largely due to cancer cell-intrinsic alterations that minimize antigenicity and/or changes in the tumor microenvironment that foster immunosuppression. Several strategies have been developed to overcome such limitations, including the use of immunostimulatory adjuvants, the co-treatment with cytotoxic anticancer therapies that enable the coordinated release of damage-associated molecular patterns, and the concomitant blockade of immune checkpoints. Personalized peptide-based vaccines are also being explored for therapeutic activity in the clinic. Here, we review recent preclinical and clinical progress in the use of peptide-based vaccines as anticancer therapeutics.Abbreviations: CMP: carbohydrate-mimetic peptide; CMV: cytomegalovirus; DC: dendritic cell; FDA: Food and Drug Administration; HPV: human papillomavirus; MDS: myelodysplastic syndrome; MHP: melanoma helper vaccine; NSCLC: non-small cell lung carcinoma; ODD: orphan drug designation; PPV: personalized peptide vaccination; SLP: synthetic long peptide; TAA: tumor-associated antigen; TNA: tumor neoantigen

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Harnessing the beneficial heterologous effects of vaccination

Cited by 222 publications

References 101 publications

Granulocyte-Monocyte Progenitors and Monocyte-Dendritic Cell Progenitors Independently Produce Functionally Distinct Monocytes

Granulocyte-Monocyte Progenitors and Monocyte-Dendritic Cell Progenitors Independently Produce Functionally Distinct Monocytes

Transfusion-related immunomodulation: a reappraisal

Trial watch: Peptide-based vaccines in anticancer therapy

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