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Immune Checkpoint Associated Acute Interstitial Nephritis

ABSTRACT: Tertiary lymphoid structure signatures are associated with immune checkpoint inhibitor related acute interstitial nephritis

PROVIDER: EGAD00010002406 | EGA |

REPOSITORIES: EGA

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Tertiary lymphoid structure signatures are associated with immune checkpoint inhibitor related acute interstitial nephritis

Project description:Tertiary lymphoid structures (TLSs) are associated with anti-tumor response following immune checkpoint inhibitor (ICI) therapy, but a commensurate observation of TLS is absent for immune related adverse events (irAEs) i.e. acute interstitial nephritis (AIN). We hypothesized that TLS-associated inflammatory gene signatures are present in AIN and performed NanoString-based gene expression and multiplex 12-chemokine profiling on paired kidney tissue, urine and plasma specimens of 36 participants who developed acute kidney injury (AKI) on ICI therapy: AIN (18), acute tubular necrosis (9), or HTN nephrosclerosis (9). Increased T and B cell scores, a Th1-CD8+ T cell axis accompanied by interferon-Ã¯ÂÂ§ and TNF superfamily signatures were detected in the ICI-AIN group. TLS signatures were significantly increased in AIN cases and supported by histopathological identification

| EGAS00001006781 | EGA

Cardiac tertiary immune niches drive immune activation in immune checkpoint inhibitor myocarditis

Project description:Cardiac tertiary immune niches drive immune activation in immune checkpoint inhibitor myocarditis

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Cardiac tertiary immune niches drive immune activation in immune checkpoint inhibitor myocarditis [CosMx]

Project description:Cardiac tertiary immune niches drive immune activation in immune checkpoint inhibitor myocarditis [CosMx]

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Immune checkpoint inhibitor-induced colitis

Project description:Immune checkpoint inhibitor-induced colitis

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Cardiac tertiary immune niches drive immune activation in immune checkpoint inhibitor myocarditis

Project description:Using integrated spatial and single-cell analyses in a pharmacological murine model, we identified regional infiltration of inflammatory myeloid cells and PD-1⁺CD8⁺ T cells in the heart that organize into fibroblast-rich immune structures, which we term Tertiary T Cell Niches (TTCNs). TTCNs serve as hubs for T cell activation, sharing features of tertiary lymphoid structures. Complementary TCR analyses revealed clonal expansion of cardiac T cells following ICI treatment. Together, these findings suggest that cardiac tertiary immune structures play a central role in activating and recruiting immune cells in ICI myocarditis and highlight pathways that could mitigate ICI cardiotoxicity.

2026-04-06 | GSE327152 | GEO

Cardiac tertiary immune niches drive immune activation in immune checkpoint inhibitor myocarditis [CosMx]

2026-04-06 | GSE326904 | GEO

Kidney Effects of Immune Checkpoint Inhibitors on a Humanized Chimeric Mouse Model.

Project description:We have employed a single cell sequencing approach using 10x Genomics scRNA-seq to study immune checkpoint inhibitor effects on kidney cells. Immune checkpoint inhibitors leads to break of immune tolerance and potential adverse related event. It is known that interstitial nephritis is most common presentation. Because exact mechanism is not clear this model wants to induce inflammation in a chimeric mouse. Evaluation of genes over or under expressed in differents groups of treatment by scRNA-seq would allow to understand better the dinamic of inflammation and identified potential targets.

2026-02-13 | GSE296138 | GEO

Late-stage tertiary lymphoid structures in hepatocellular carcinoma treated with neoadjuvant immune checkpoint blockade

Project description:Late-stage tertiary lymphoid structures in hepatocellular carcinoma treated with neoadjuvant immune checkpoint blockade

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IL-17A Neutralization Prevents Immune Checkpoint Inhibitor-Associated Myocarditis and Synergistically Enhances Immune Checkpoint Blockade Therapy

Project description:IL-17A Neutralization Prevents Immune Checkpoint Inhibitor-Associated Myocarditis and Synergistically Enhances Immune Checkpoint Blockade Therapy

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Fibroblastic reticular cells serve as primary immune checkpoint in visceral adipose tissues and secure peritoneal immunity

Project description:Immune protection of the body cavities depends on the swift activation of innate and adaptive immune responses in non-classical secondary lymphoid organs known as fat-associated lymphoid clusters (FALCs). While it is well-established that fibroblastic reticular cells (FRCs) are an integral component of the immune-stimulating infrastructure of lymph nodes and other classical secondary lymphoid organs, it has remained elusive whether and how FRCs in FALCs contribute to peritoneal immunity. Using FRC-specific gene targeting, we found that FALCs are underpinned by an elaborated FRC network and that initiation of peritoneal immunity was governed through FRC activation via MyD88-dependent innate immunological sensing. FRC-specific ablation of Myd88 expression blocked recruitment of inflammatory monocytes into FALCs and subsequent CD4+ T cell-dependent B-cell activation. Moreover, containment of Salmonella infection was compromised in conditionally Myd88-deficient mice indicating that FRCs in FALCs function as initial checkpoint in the orchestration of protective immune responses in the peritoneal cavity.

2018-06-12 | E-MTAB-6886 | biostudies-arrayexpress

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