Quiescent Tissue Stem Cells Evade Immune Surveillance

Agudo, Judith; Park, Eun Sook; Rose, Samuel A.; Alibo, Eziwoma; Sweeney, Robert E.; Dhainaut, Maxime; Kobayashi, Koichi S.; Sachidanandam, Ravi; Baccarini, Alessia; Mérad, Miriam; Brown, Brian D.

doi:10.1016/j.immuni.2018.02.001

Cited by 175 publications

(174 citation statements)

References 60 publications

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“…To overcome this limitation, we took advantage of just eGFP death inducing (Jedi) T cells, which express a T cell receptor that recognizes the immunodominant epitope of GFP loaded in the H-2Kd allele of MHC-I (Agudo et al, 2015). Jedi T cells enable GFP to be used as a model antigen that can be easily detected (Agudo et al, 2018). We engineered 4T1 to express either GFP (4T1-GFP) or near-infrared fluorescent protein 670 (4T1-RFP) alone, or with Cas9 (4T1-Cas9-GFP and 4T1-Cas9-RFP).…”

Section: Resultsmentioning

confidence: 99%

Protein Barcodes Enable High-Dimensional Single-Cell CRISPR Screens

Wroblewska

Dhainaut

Ben-Zvi

et al. 2018

Cell

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113

100

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Summary CRISPR pools are being widely employed to identify gene functions. However, current technology, which utilizes DNA as barcodes, permits limited phenotyping and bulk-cell resolution. To enable novel screening capabilities, we developed a barcoding system operating at the protein level. We synthesized modules encoding triplet combinations of linear epitopes to generate >100 unique protein barcodes (Pro-Codes). ProCode-expressing vectors were introduced into cells and analyzed by CyTOF mass-cytometry. Using just 14 antibodies, we detected 364 Pro-Code populations; establishing the largest set of protein-based reporters. By pairing each Pro-Code with a different CRISPR, we simultaneously analyzed multiple phenotypic markers, including phospho-signaling, on dozens of knockouts. Pro-Code/CRISPR screens found two interferon-stimulated genes, the immunoproteasome component Psmb8 and a chaperone Rtp4, are important for antigen-dependent immune editing of cancer cells, and identified Socs1 as a negative regulator of Pd-l1. The Pro-Code technology enables simultaneous high-dimensional protein-level phenotyping of 100s of genes with single cell resolution.

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Section: Resultsmentioning

confidence: 99%

Protein Barcodes Enable High-Dimensional Single-Cell CRISPR Screens

Wroblewska

Dhainaut

Ben-Zvi

et al. 2018

Cell

Self Cite

113

100

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“…Agudo and colleagues recently uncovered that a stem cell’s immune privilege status is linked to its level of activity (Agudo et al, 2018). Like most tissue cells, cycling stem cells of the intestine, ovary and mammary gland display major histocompatibility class I (MHC-I) as well as an array of cytokine receptors on their surface.…”

Section: Introductionmentioning

confidence: 99%

Two to Tango: Dialog between Immunity and Stem Cells in Health and Disease

Naik

Larsen

Cowley

et al. 2018

Cell

189

144

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Summary Stem cells regenerate tissues in homeostasis and under stress. By taking cues from their microenvironment or “niche”, they smoothly transition between these states. Immune cells have surfaced as prominent members of stem cell niches across the body. Here, we draw parallels between different stem cell niches to explore the context-specific interactions that stem cells have with tissue resident and recruited immune cells. We also highlight stem cells’ innate ability to sense and respond to stress, and the enduring memory that forms from such encounters. This fascinating crosstalk holds great promise for novel therapies in inflammatory diseases and regenerative medicine.

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“…Surprisingly, Treg cells were in dynamic equilibrium with hair‐regrowth phases, and influenced follicular stem cell quiescence by expression of the Notch1 ligand Jagged 1. Similarly, Treg cells play an active role in protecting the intestinal epithelial, and bone marrow stem cell niche . Finally, tissue‐resident Treg cells also express certain genes involved in epithelial cell repair, such as the growth factor amphiregulin ( Areg ), and thereby contribute to wound healing.…”

Section: Introductionmentioning

confidence: 99%

Regulation of regulatory T cells in cancer

2019

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Summary The inflammatory response to transformed cells forms the cornerstone of natural or therapeutically induced protective immunity to cancer. Regulatory T (Treg) cells are known for their critical role in suppressing inflammation, and therefore can antagonize effective anti‐cancer immune responses. As such, Treg cells can play detrimental roles in tumour progression and in the response to both conventional and immune‐based cancer therapies. Recent advances in our understanding of Treg cells reveal complex niche‐specific regulatory programmes and functions, which are likely to extrapolate to cancer. The regulation of Treg cells is reliant on upstream cues from haematopoietic and non‐immune cells, which dictates their genetic, epigenetic and downstream functional programmes. In this review we will discuss how Treg cells are themselves regulated in normal and transformed tissues, and the implications of this cross talk on tumour growth.

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Quiescent Tissue Stem Cells Evade Immune Surveillance

Cited by 175 publications

References 60 publications

Protein Barcodes Enable High-Dimensional Single-Cell CRISPR Screens

Protein Barcodes Enable High-Dimensional Single-Cell CRISPR Screens

Two to Tango: Dialog between Immunity and Stem Cells in Health and Disease

Regulation of regulatory T cells in cancer

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