IMMUNOLOGY2026™ Conference Recordings For Attendees-Overcoming tumor-intrinsic immunotherapy resistance with hypofractionated radiotherapy

Overcoming tumor-intrinsic immunotherapy resistance with hypofractionated radiotherapy

Video Transcription

Video Summary

The speaker described research showing that radiotherapy, especially a hypofractionated 6 Gy schedule, can make tumors more immunogenic and help overcome resistance to immunotherapy. Using melanoma models lacking interferon-gamma receptor 1, the team found these tumors were resistant to interferon-gamma signaling and to checkpoint blockade such as anti-CTLA-4 and anti-PD-1. They showed that hypofractionated radiation increased tumor-infiltrating CD4 and CD8 T cells, improved their function, and reduced regulatory T cells and myeloid-derived suppressor cells. However, the effect was weaker in interferon-gamma receptor–knockout tumors because radiation could no longer deplete Tregs effectively. Combining radiation with ruxolitinib modestly helped, but the strongest immune activation came from combining radiation with anti-CTLA-4, which slightly improved survival. The speaker concluded that tumor-intrinsic interferon-gamma signaling is important for radiation-driven immune remodeling and may help resensitize resistant tumors to checkpoint therapy.

Meta Tag

Date April 19, 2026 10:15 AM - 10:30 AM

Room 156

Session Immune Cells in the Tumor Microenvironment III

Speaker Lewis Shi

Track Tumor Immunology: Cellular Responses and Tumor Microenvironment (TIME)

Year 2026

Keywords

radiotherapy

hypofractionated radiation

interferon-gamma receptor 1

checkpoint blockade

melanoma immunotherapy

April 19, 2026 10:15 AM - 10:30 AM

156

Immune Cells in the Tumor Microenvironment III

Lewis Shi

Tumor Immunology: Cellular Responses and Tumor Microenvironment (TIME)

2026