IMMUNOLOGY2026™ Conference Recordings For Attendees-Liver metastasis limits immunotherapy efficacy by dismantling systemic anti-tumor T cell responses through unconventional antigen presentation

Liver metastasis limits immunotherapy efficacy by dismantling systemic anti-tumor T cell responses through unconventional antigen presentation

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Video Summary

Debolina Ganguly presented research showing that liver metastases can suppress the body&rsquo;s overall anti-tumor immune response and reduce the effectiveness of checkpoint immunotherapy. Clinical data from melanoma, lung cancer, and breast cancer patients showed worse outcomes when liver metastases were present. In mouse models, liver metastasis caused distant primary tumors to stop responding to anti-PD-1 treatment, unlike lung metastasis. This effect was antigen-specific and linked to increased regulatory T cells and loss of CD8 T cells. The team identified an unconventional tolerogenic antigen-presenting cell in the liver: liver sinusoidal endothelial cells (LSECs), which present antigen with low co-stimulation and high TGF-beta, promoting immune tolerance. Activating dendritic cells with a TLR3 agonist plus anti-PD-1 reversed this tolerance, restored CD8 T-cell function, reduced Tregs, and improved tumor response systemically.

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Date April 16, 2026 1:15 PM - 1:30 PM

Room 153AB

Session Antigen Presentation in Immunity, Pathology, and Tolerance

Speaker Debolina Ganguly

Track Classical and Non-Classical Antigen Presenting Cells (APC)

Year 2026

Keywords

liver metastases

checkpoint immunotherapy

anti-PD-1 resistance

liver sinusoidal endothelial cells

CD8 T-cell suppression

April 16, 2026 1:15 PM - 1:30 PM

153AB

Antigen Presentation in Immunity, Pathology, and Tolerance

Debolina Ganguly

Classical and Non-Classical Antigen Presenting Cells (APC)

2026