Immunity

Journal: Immunity

Publisher

Cell Press

ISSN

1074-7613
1097-4180

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Publications1 - 10 of 33

Diet-derived LPS determines intestinal IgA induction and repertoire characteristics independently of the microbiota
Mooser, Catherine; Ronchi, Francesca; Limenitakis, Julien P.; et al. (2025)
Immunity
A hallmark of the main secreted antibody immunoglobulin A (IgA) is its mutational load that accumulates throughout life. Although this is mainly interpreted in terms of continuing microbial induction, we show that dietary composition during early life can promote IgA induction, its repertoire, and mutational diversification independently of microbial exposure. Using germ-free and colonized mice fed different diets formulated with proprietary grain-based processing or from purified chemicals with different principal macronutrient calorie sources, we found that dietary lipopolysaccharide contamination led to Toll-like receptor (TLR) 4 signaling and promoted germinal center activity in the intestinal immune compartment. The effects of lipopolysaccharide on mucosal immune induction were phenocopied only when presented within colloidal liposomes rather than in dispersed solution. These findings indicate that dietary composition and its formulation can leave a durable impression on the resultant IgA repertoire.
From Vaccines to Memory and Back
Sallusto, Federica; Lanzavecchia, Antonio; Araki, Koichi; et al. (2010)
Immunity
Interleukin-33-Activated Islet-Resident Innate Lymphoid Cells Promote Insulin Secretion through Myeloid Cell Retinoic Acid Production
Dalmas, Elise; Lehmann, Frank M.; Dror, Erez; et al. (2017)
Immunity
High-throughput T cell receptor engineering by functional screening identifies candidates with enhanced potency and specificity
Vazquez-Lombardi, Rodrigo; Jung, Johanna S.; Schlatter, Fabrice S.; et al. (2022)
Immunity
A major challenge in adoptive T cell immunotherapy is the discovery of natural T cell receptors (TCRs) with high activity and specificity to tumor antigens. Engineering synthetic TCRs for increased tumor antigen recognition is complicated by the risk of introducing cross-reactivity and by the poor correlation that can exist between binding affinity and activity of TCRs in response to antigen (peptide-MHC). Here, we developed TCR-Engine, a method combining genome editing, computational design, and deep sequencing to engineer the functional activity and specificity of TCRs on the surface of a human T cell line at high throughput. We applied TCR-Engine to successfully engineer synthetic TCRs for increased potency and specificity to a clinically relevant tumor-associated antigen (MAGE-A3) and validated their translational potential through multiple in vitro and in vivo assessments of safety and efficacy. Thus, TCR-Engine represents a valuable technology for engineering of safe and potent synthetic TCRs for immunotherapy applications.
An unexpected connection
Halin, Cornelia; Detmar, Michael (2006)
Immunity
Expression of the membrane tetraspanin claudin 18 on cancer cells promotes T lymphocyte infiltration and antitumor immunity in pancreatic cancer
De Sanctis, Francesco; Dusi, Silvia; Caligola, Simone; et al. (2024)
Immunity
Tumors weakly infiltrated by T lymphocytes poorly respond to immunotherapy. We aimed to unveil malignancy-associated programs regulating T cell entrance, arrest, and activation in the tumor environment. Differential expression of cell adhesion and tissue architecture programs, particularly the presence of the membrane tetraspanin claudin (CLDN)18 as a signature gene, demarcated immune-infiltrated from immune-depleted mouse pancreatic tumors. In human pancreatic ductal adenocarcinoma (PDAC) and non-small cell lung cancer, CLDN18 expression positively correlated with more differentiated histology and favorable prognosis. CLDN18 on the cell surface promoted accrual of cytotoxic T lymphocytes (CTLs), facilitating direct CTL contacts with tumor cells by driving the mobilization of the adhesion protein ALCAM to the lipid rafts of the tumor cell membrane through actin. This process favored the formation of robust immunological synapses (ISs) between CTLs and CLDN18-positive cancer cells, resulting in increased T cell activation. Our data reveal an immune role for CLDN18 in orchestrating T cell infiltration and shaping the tumor immune contexture.
Mitochondrial DNA released by senescent tumor cells enhances PMN-MDSC-driven immunosuppression through the cGAS-STING pathway
Lai, Ping; Liu, Lei; Bancaro, Nicolò; et al. (2025)
Immunity
Mitochondrial dysfunction is a hallmark of cellular senescence. Here, we investigated whether senescent cells release mitochondrial (mt)DNA into the extracellular space and its impact on innate immunity. We found that both primary senescent cells and tumor cells undergoing therapy-induced senescence actively released mtDNA into the extracellular environment. mtDNA released by senescent cells was packaged within extracellular vesicles and selectively transferred to polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) in the tumor microenvironment. Upon uptake, extracellular mtDNA enhanced the immunosuppressive activity of PMN-MDSCs via cGAS-STING-NF-κB signaling, thereby promoting tumor progression. While STING activation directly induced NF-κB signaling, it also activated PKR-like endoplasmic reticulum kinase (PERK), which further amplified NF-κB activity, in PMN-MDSCs. mtDNA release from senescent cells was mediated by voltage-dependent anion channels (VDACs), and pharmacological inhibition of VDAC reduced extracellular mtDNA levels, reversed PMN-MDSC-driven immunosuppression, and enhanced chemotherapy efficacy in prostate cancer mouse models. These findings suggest that targeting mtDNA release could reprogram the immunosuppressive tumor microenvironment, improving therapeutic outcomes for chemotherapy-treated patients.
Interleukin-2 immunotherapy reveals human regulatory T cell subsets with distinct functional and tissue-homing characteristics
Raeber, Miro E.; Caspar, Dominic P.; Zurbuchen, Yves; et al. (2024)
Immunity
Due to its stimulatory potential for immunomodulatory CD4⁺ regulatory T (Treg) cells, low-dose interleukin-2 (IL-2) immunotherapy has gained considerable attention for the treatment of autoimmune diseases. In this investigator-initiated single-arm non-placebo-controlled phase-2 clinical trial of low-dose IL-2 immunotherapy in systemic lupus erythematosus (SLE) patients, we generated a comprehensive atlas of in vivo human immune responses to low-dose IL-2. We performed an in-depth study of circulating and cutaneous immune cells by imaging mass cytometry, high-parameter flow cytometry, transcriptomics, and targeted serum proteomics. Low-dose IL-2 stimulated various circulating immune cells, including Treg cells with a skin-homing phenotype that appeared in the skin of SLE patients in close interaction with endothelial cells. Analysis of surface proteins and transcriptomes revealed different IL-2-driven Treg cell activation programs, including gut-homing CD38⁺, skin-homing HLA-DR⁺, and highly proliferative inflammation-homing CD38⁺ HLA-DR⁺ Treg cells. Collectively, these data define the distinct human Treg cell subsets that are responsive to IL-2 immunotherapy.
Infected Cell in Trouble
Hardt, Wolf-Dietrich (2010)
Immunity
tEMPting Fate MaYBe the Solution
Schneider, Christoph; Kopf, Manfred (2015)
Immunity

Publications1 - 10 of 33

Journal: Immunity

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