Modulating the polyamine/hypusine axis controls generation of CD8+ tissue-resident memory T cells

Elmarsafawi, Aya G.; Hesterberg, Rebecca S.; Fernandez, Mario R.; Yang, Chunying; Darville, Lancia; Liu, Min; Koomen, John M.; Phanstiel, Otto; Atkins, Reginald; Mullinax, John E.; Pilon‐Thomas, Shari; Locke, Frederick L.; Epling-Burnette, Pearlie K.; Cleveland, John L.

doi:10.1172/jci.insight.169308

Cited by 9 publications

(2 citation statements)

References 48 publications

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“…TCR activation in CD4 + T-cells is mediated by the conversion of arginine into ornithine, and the proliferation and activity of T-cells following TCR activation is fully dependent on an increased polyamine pool [ 76 , 77 , 82 ]. A recent finding of Elmarsafawi et al suggests that glutamine is the primary carbon source for polyamines in antigen-activated effector CD8 + T-cells [ 83 ]. These data indicate that different subpopulations of immune cells vary in their preferred carbon source for polyamine biosynthesis, thereby competing with tumor cells for both major polyamine precursors.…”

Section: Polyamines and Cells Of The Tmementioning

confidence: 99%

Polyamines: the pivotal amines in influencing the tumor microenvironment

Holbert,

Casero,

Stewart

2024

Discov Onc

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Cellular proliferation, function and survival is reliant upon maintaining appropriate intracellular polyamine levels. Due to increased metabolic needs, cancer cells elevate their polyamine pools through coordinated metabolism and uptake. High levels of polyamines have been linked to more immunosuppressive tumor microenvironments (TME) as polyamines support the growth and function of many immunosuppressive cell types such as MDSCs, macrophages and regulatory T-cells. As cancer cells and other pro-tumorigenic cell types are highly dependent on polyamines for survival, pharmacological modulation of polyamine metabolism is a promising cancer therapeutic strategy. This review covers the roles of polyamines in various cell types of the TME including both immune and stromal cells, as well as how competition for nutrients, namely polyamine precursors, influences the cellular landscape of the TME. It also details the use of polyamines as biomarkers and the ways in which polyamine depletion can increase the immunogenicity of the TME and reprogram tumors to become more responsive to immunotherapy.

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Section: Polyamines and Cells Of The Tmementioning

confidence: 99%

Polyamines: the pivotal amines in influencing the tumor microenvironment

Holbert,

Casero,

Stewart

2024

Discov Onc

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“…Spermidine was shown to prevent TCR clustering on the cell membrane by cholesterol depletion to inhibit CD8 + T-cell activation ( 82 ). Furthermore, spermidine and hypusination of eIF5A in effector CD8 + T-cells prevented the formation of tissue-resident memory CD8 + T-cells and reduced the production of the pro-inflammatory cytokines TNF-α and IFN-γ ( 83 ).…”

Section: The Role Of Secreted Factors On Myeloid-lymphocyte Crosstalkmentioning

confidence: 99%

Crosstalk between efferocytic myeloid cells and T-cells and its relevance to atherosclerosis

Ngai,

Sukka,

Tabas

2024

Front. Immunol.

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The interplay between myeloid cells and T-lymphocytes is critical to the regulation of host defense and inflammation resolution. Dysregulation of this interaction can contribute to the development of chronic inflammatory diseases. Important among these diseases is atherosclerosis, which refers to focal lesions in the arterial intima driven by elevated apolipoprotein B-containing lipoproteins, notably low-density lipoprotein (LDL), and characterized by the formation of a plaque composed of inflammatory immune cells, a collection of dead cells and lipids called the necrotic core, and a fibrous cap. As the disease progresses, the necrotic core expands, and the fibrous cap becomes thin, which increases the risk of plaque rupture or erosion. Plaque rupture leads to a rapid thrombotic response that can give rise to heart attack, stroke, or sudden death. With marked lowering of circulating LDL, however, plaques become more stable and cardiac risk is lowered—a process known as atherosclerosis regression. A critical aspect of both atherosclerosis progression and regression is the crosstalk between innate (myeloid cells) and adaptive (T-lymphocytes) immune cells. Myeloid cells are specialized at clearing apoptotic cells by a process called efferocytosis, which is necessary for inflammation resolution. In advanced disease, efferocytosis is impaired, leading to secondary necrosis of apoptotic cells, inflammation, and, most importantly, defective tissue resolution. In regression, efferocytosis is reawakened aiding in inflammation resolution and plaque stabilization. Here, we will explore how efferocytosing myeloid cells could affect T-cell function and vice versa through antigen presentation, secreted factors, and cell-cell contacts and how this cellular crosstalk may contribute to the progression or regression of atherosclerosis.

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Unlocking the full potential of memory T cells in adoptive T cell therapy for hematologic malignancies

Sun,

Hu,

et al. 2025

International Immunopharmacology

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Modulating the polyamine/hypusine axis controls generation of CD8+ tissue-resident memory T cells

Cited by 9 publications

References 48 publications

Polyamines: the pivotal amines in influencing the tumor microenvironment

Polyamines: the pivotal amines in influencing the tumor microenvironment

Crosstalk between efferocytic myeloid cells and T-cells and its relevance to atherosclerosis

Unlocking the full potential of memory T cells in adoptive T cell therapy for hematologic malignancies

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