Magnesium sensing via LFA-1 regulates CD8+ T cell effector function

Lötscher, Jonas; Líndez, Adrià-Arnau Martí i; Kirchhammer, Nicole; Cribioli, Elisabetta; Giordano, Greta; Trefny, Marcel P.; Lenz, Markus; Rothschild, Sacha I.; Strati, Paolo; Künzli, Marco; Claudia, Lotter,; Schenk, Susanne; Dehio, Philippe; Löliger, Jordan; Litzler, Ludivine C.; Schreiner, David; Koch, Victoria; Pagé, Nicolas; Lee, Dahye; Grählert, Jasmin; Kuzmin, Dmitry; Burgener, Anne‐Valérie; Merkler, Doron; Pless, Miklos; Balmer, Maria L.; Reith, Walter; Huwyler, Jörg; Irving, Melita; King, Catrina E.; Zippelius, Alfred; Hess, Christoph

doi:10.1016/j.cell.2021.12.039

Cited by 127 publications

(77 citation statements)

References 65 publications

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“…1 a). Notably, magnesium cations (Mg 2+ )—a stimulator of the adaptive immune system—were added to the hydrogel to enhance the immunomodulatory activity of the hydrogel [ 41 , 42 ]. The as-prepared α-PDL1/PEIGel was semitransparent and estimated to contain 85% water mass ( Fig.…”

Section: Resultsmentioning

confidence: 99%

PEIGel: A biocompatible and injectable scaffold with innate immune adjuvanticity for synergized local immunotherapy

Xiao

Wang

et al. 2022

Materials Today Bio

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Section: Resultsmentioning

confidence: 99%

PEIGel: A biocompatible and injectable scaffold with innate immune adjuvanticity for synergized local immunotherapy

Xiao

Wang

et al. 2022

Materials Today Bio

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“…Notably, others have also reported an increase in Mg 2+ concentration in pregnant women with COVID-19 ( Anuk et al, 2021 ) and high levels of serum Mg 2+ ions were observed in kidney transplant patients positive to Helicobacter pylori ( Hafizi et al, 2014 ) and with visceral leishmaniasis infectious disease ( Lal et al, 2013 ) indicating a possible role of Mg 2+ in infectious illness. Increased serum Mg 2+ ions could either be a cause of renal failure ( Azem et al, 2020 ) or a physiological attempt to induce the adaptive immune response through the metal’s binding on the co-stimulatory cell-surface molecule LFA-1, which requires Mg 2+ to adopt its active conformation on CD8 + T cells ( Lötscher et al, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

Inflammatory-Metal Profile as a Hallmark for COVID-19 Severity During Pregnancy

Vásquez-Procopio

Espejel-Núñez

Torres-Torres

et al. 2022

Front. Cell Dev. Biol.

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Pregnancy makes women more susceptible to infectious agents; however, available data on the effect of SARS-CoV-2 on pregnant women are limited. To date, inflammatory responses and changes in serum metal concentration have been reported in COVID-19 patients, but few associations between metal ions and cytokines have been described. The aim of this study was to evaluate correlations between inflammatory markers and serum metal ions in third-trimester pregnant women with varying COVID-19 disease severity. Patients with severe symptoms had increased concentrations of serum magnesium, copper, and calcium ions and decreased concentrations of iron, zinc, and sodium ions. Potassium ions were unaffected. Pro-inflammatory cytokines IL-6, TNF-α, IL-8, IL-1α, anti-inflammatory cytokine IL-4, and the IP-10 chemokine were induced in the severe presentation of COVID-19 during pregnancy. Robust negative correlations between iron/magnesium and zinc/IL-6, and a positive correlation between copper/IP-10 were observed in pregnant women with the severe form of the disease. Thus, coordinated alterations of serum metal ions and inflammatory markers – suggestive of underlying pathophysiological interactions—occur during SARS-CoV-2 infection in pregnancy.

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“…Under low Mg 2+ levels, CAR T-cell activation and cytotoxicity against tumor cells were considerably reduced. Most importantly, in lymphoma patients treated with CD19 CAR T cells, low serum magnesium levels correlated with poor prognosis [ 113 ]. The importance of ICAM-1 expression on cancer cells for CAR T-cell activation was revealed in a CRISPR-based screen performed in a multiple myeloma cell line.…”

Section: Adhesion Molecules Controlling the Contact Between Car T Cel...mentioning

confidence: 99%

Immune Checkpoint Proteins, Metabolism and Adhesion Molecules: Overlooked Determinants of CAR T-Cell Migration?

Simula

Ollivier

Icard

et al. 2022

Cells

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Adoptive transfer of T cells genetically engineered to express chimeric antigen receptors (CAR) has demonstrated striking efficacy for the treatment of several hematological malignancies, including B-cell lymphoma, leukemia, and multiple myeloma. However, many patients still do not respond to this therapy or eventually relapse after an initial remission. In most solid tumors for which CAR T-cell therapy has been tested, efficacy has been very limited. In this context, it is of paramount importance to understand the mechanisms of tumor resistance to CAR T cells. Possible factors contributing to such resistance have been identified, including inherent CAR T-cell dysfunction, the presence of an immunosuppressive tumor microenvironment, and tumor-intrinsic factors. To control tumor growth, CAR T cells have to migrate actively enabling a productive conjugate with their targets. To date, many cells and factors contained within the tumor microenvironment have been reported to negatively control the migration of T cells and their ability to reach cancer cells. Recent evidence suggests that additional determinants, such as immune checkpoint proteins, cellular metabolism, and adhesion molecules, may modulate the motility of CAR T cells in tumors. Here, we review the potential impact of these determinants on CAR T-cell motility, and we discuss possible strategies to restore intratumoral T-cell migration with a special emphasis on approaches targeting these determinants.

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Magnesium sensing via LFA-1 regulates CD8+ T cell effector function

Cited by 127 publications

References 65 publications

PEIGel: A biocompatible and injectable scaffold with innate immune adjuvanticity for synergized local immunotherapy

PEIGel: A biocompatible and injectable scaffold with innate immune adjuvanticity for synergized local immunotherapy

Inflammatory-Metal Profile as a Hallmark for COVID-19 Severity During Pregnancy

Immune Checkpoint Proteins, Metabolism and Adhesion Molecules: Overlooked Determinants of CAR T-Cell Migration?

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