Indoleamine 2,3-dioxygenase 1 is essential for sustaining durable antibody responses

Lightman, Shivana M.; Peresie, Jennifer; Carlson, Louise; Holling, G. Aaron; Honikel, Mackenzie; Chavel, Colin A.; Nemeth, Michael J.; Olejniczak, Scott H.; Lee, Kelvin P.

doi:10.1016/j.immuni.2021.10.005

Cited by 8 publications

(9 citation statements)

References 73 publications

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“…These mechanisms are generally divided into two categories: (i) cancer cell-intrinsic mechanisms, such as loss of tumor antigens or antigen presentation and IFN-γ sensing deficiency, and (ii) cancer cell-extrinsic mechanisms, which promote an immunosuppressive microenvironment, including reductions in the function or number of CD8 + T cells, an increase in the number of T regs or M2-like tumor-associated macrophages, and the production of immunosuppressive cytokines. In addition to these elucidated mechanisms, other mechanisms must exist to explain many cases for which the cause of insensitivity remains unknown (59,(63)(64)(65)(66)(67)(68)(69)(70)(71). Our results are not only consistent with previous reports but also expand on the proposed roles for EMP as an important mechanism of immune evasion (4).…”

Section: Discussionsupporting

confidence: 92%

Genome-wide CRISPR screens define determinants of epithelial-mesenchymal transition mediated immune evasion by pancreatic cancer cells

Zhang

Camps

et al. 2023

Sci. Adv.

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The genetic circuits that allow cancer cells to evade immune killing via epithelial mesenchymal plasticity remain poorly understood. Here, we showed that mesenchymal-like (Mes) KPC3 pancreatic cancer cells were more resistant to cytotoxic T lymphocyte (CTL)–mediated killing than the parental epithelial–like (Epi) cells and used parallel genome-wide CRISPR screens to assess the molecular underpinnings of this difference. Core CTL-evasion genes (such as IFN-γ pathway components) were clearly evident in both types. Moreover, we identified and validated multiple Mes-specific regulators of cytotoxicity, such as Egfr and Mfge8. Both genes were significantly higher expressed in Mes cancer cells, and their depletion sensitized Mes cancer cells to CTL-mediated killing. Notably, Mes cancer cells secreted more Mfge8 to inhibit proliferation of CD8 + T cells and production of IFN-γ and TNFα. Clinically, increased Egfr and Mfge8 expression was correlated with a worse prognosis. Thus, Mes cancer cells use Egfr-mediated intrinsic and Mfge8-mediated extrinsic mechanisms to facilitate immune escape from CD8 + T cells.

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Section: Discussionsupporting

confidence: 92%

Genome-wide CRISPR screens define determinants of epithelial-mesenchymal transition mediated immune evasion by pancreatic cancer cells

Zhang

Camps

et al. 2023

Sci. Adv.

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“…Moreover, blockade of the adhesion molecule integrin ⍺4b1 causes the egress and loss of long-lived plasma cells (DiLillo et al, 2008). In addition, certain survival signals, such CD80/ CD86-mediated engagement of CD28 on plasma cells and activation of aryl hydrocarbon receptor signaling, seem to occur uniquely in the bone marrow (Lightman et al, 2021;Rozanski et al, 2011). Together, there is little consensus on the details of how plasma cell survival is supported extrinsically.…”

Section: Cell-extrinsic Control Of Plasma Cell Lifespanmentioning

confidence: 99%

Instructing durable humoral immunity for COVID-19 and other vaccinable diseases

Bhattacharya

2022

Immunity

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“…This is evident in lung cancer where myeloid-derived suppressor cells' (MDSCs) induction of IDO leads to kynurenine that activates the AhR to induce Breg and immune suppression [170]. In long-lived plasma cells, the kynurenine activation of the AhR is essential to their longevity and function [171]. Overall, such data highlight the relevance, and complexity, of AhR effects in humoral immunity.…”

Section: B-cells and Metabolismmentioning

confidence: 99%

Redefining Autoimmune Disorders’ Pathoetiology: Implications for Mood and Psychotic Disorders’ Association with Neurodegenerative and Classical Autoimmune Disorders

Anderson¹,

Almulla

Reíter

et al. 2023

Cells

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Although previously restricted to a limited number of medical conditions, there is a growing appreciation that ‘autoimmune’ (or immune-mediated) processes are important aspects of a wide array of diverse medical conditions, including cancers, neurodegenerative diseases and psychiatric disorders. All of these classes of medical conditions are associated with alterations in mitochondrial function across an array of diverse cell types. Accumulating data indicate the presence of the mitochondrial melatonergic pathway in possibly all body cells, with important consequences for pathways crucial in driving CD8+ T cell and B-cell ‘autoimmune’-linked processes. Melatonin suppression coupled with the upregulation of oxidative stress suppress PTEN-induced kinase 1 (PINK1)/parkin-driven mitophagy, raising the levels of the major histocompatibility complex (MHC)-1, which underpins the chemoattraction of CD8+ T cells and the activation of antibody-producing B-cells. Many factors and processes closely associated with autoimmunity, including gut microbiome/permeability, circadian rhythms, aging, the aryl hydrocarbon receptor, brain-derived neurotrophic factor (BDNF) and its receptor tyrosine receptor kinase B (TrkB) all interact with the mitochondrial melatonergic pathway. A number of future research directions and novel treatment implications are indicated for this wide collection of poorly conceptualized and treated medical presentations. It is proposed that the etiology of many ‘autoimmune’/‘immune-mediated’ disorders should be conceptualized as significantly determined by mitochondrial dysregulation, with alterations in the mitochondrial melatonergic pathway being an important aspect of these pathoetiologies.

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Indoleamine 2,3-dioxygenase 1 is essential for sustaining durable antibody responses

Cited by 8 publications

References 73 publications

Genome-wide CRISPR screens define determinants of epithelial-mesenchymal transition mediated immune evasion by pancreatic cancer cells

Genome-wide CRISPR screens define determinants of epithelial-mesenchymal transition mediated immune evasion by pancreatic cancer cells

Instructing durable humoral immunity for COVID-19 and other vaccinable diseases

Redefining Autoimmune Disorders’ Pathoetiology: Implications for Mood and Psychotic Disorders’ Association with Neurodegenerative and Classical Autoimmune Disorders

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