IMMUNOLOGY2026™ Conference Recordings For Attendees-T-cell Signaling and Engineering

Video Transcription

Video Summary

The speaker presented recent work on LAG-3 biology, focusing on how LAG-3 checkpoint signaling is activated. They showed that ligand engagement triggers rapid, non-K48 polyubiquitination of LAG-3 at a conserved lysine, and that this modification is blocked by the anti-LAG-3 antibody relatlimab. Ubiquitination did not cause degradation; instead, it was required for LAG-3’s inhibitory function. The Cbl family proteins, Cbl-c and Cbl-b, redundantly mediated this ubiquitination. Mechanistically, ubiquitination appears to release the LAG-3 intracellular signaling motif from the plasma membrane, enabling downstream inhibitory signaling. Mouse studies confirmed that loss of this ubiquitination impairs LAG-3 function and enhances anti-tumor immunity when combined with anti-PD-1 therapy. The group also proposed LAG-3 ubiquitination as a biomarker for patient stratification and reported that a LAG-3 agonist promotes both inhibition and ubiquitination.

Meta Tag

Date April 18, 2026 10:57 AM - 11:15 AM

Room 153C

Session A New Era in Interdisciplinary Immunotherapy, Sponsored by the Chinese Soc. for Immunol. (CSI)

Speaker Haopeng Wang

Track Translational and Interventional Immunology (TI)

Year 2026

Keywords

LAG-3

ubiquitination

checkpoint signaling

relatlimab

Cbl-b Cbl-c

April 18, 2026 10:57 AM - 11:15 AM

153C

A New Era in Interdisciplinary Immunotherapy, Sponsored by the Chinese Soc. for Immunol. (CSI)

Haopeng Wang

Translational and Interventional Immunology (TI)

2026