IMMUNOLOGY2026™ Conference Recordings For Attendees-Early chromatin and transcriptional changes driven by NFAT and its transcriptional partners in 'exhausted' CD8+ T cells

Early chromatin and transcriptional changes driven by NFAT and its transcriptional partners in 'exhausted' CD8+ T cells

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The speaker discussed recent work on CD8 T-cell exhaustion in tumors, focusing on how chromatin and transcriptional changes drive T cells away from effective tumor killing. In melanoma tumor-infiltrating lymphocytes (TILs), exhaustion begins very early after tumor entry: T cells show reduced cytokine production, increased inhibitory receptors like PD-1 and TIM-3, and early exhaustion-associated gene expression, including NR4A factors and TOX.<br /><br />A key finding was that NFAT, activated by calcium/calcineurin signaling, initiates early chromatin opening across the genome and at the TOX locus. These openings are rapid, NFAT-dependent, and associated with enhancer activation, but are initially reversible. The team then used an in vitro ionomycin pulse model to mimic early exhaustion and found that many exhaustion-related genes, including TOX, are induced through NFAT.<br /><br />To identify NFAT partners, they used TurboID proteomics and found several transcription factors, notably FOSL2. FOSL2 is upregulated in TILs and cooperates with NFAT to enhance exhaustion-gene expression and enhancer activation, including at the TIM-3 locus. Overall, the talk emphasized that exhaustion is not a single program but a collection of pathways, suggesting future therapeutic opportunities to selectively modulate harmful exhaustion features while preserving T-cell survival in tumors.

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Date April 17, 2026 9:21 AM - 9:54 AM

Room 253

Session Major Symposium C: Epigenetic Modifiers as Drivers of Immune Function

Speaker Patrick Hogan

Track Innate Immune Responses and Host Defense: Molecular Mechanisms (INM)

Year 2026

Keywords

CD8 T-cell exhaustion

tumor-infiltrating lymphocytes

NFAT signaling

chromatin opening

TOX

FOSL2

melanoma

April 17, 2026 9:21 AM - 9:54 AM

253

Major Symposium C: Epigenetic Modifiers as Drivers of Immune Function

Patrick Hogan

Innate Immune Responses and Host Defense: Molecular Mechanisms (INM)

2026