Highlights of IMMUNOLOGY2026™ - Invited Program Recordings-Spatial and metabolic guidance on tailoring anti-tumor immunity

Video Transcription

Video Summary

Dr. Ping-Chi Ho received the 2026 AAI BD Biosciences Investigator Award for his influential work in tumor immunology and immunometabolism. After a brief introduction to his background and career path, Dr. Ho thanked the AAI community and described how his early training and mentorship helped launch his research.<br /><br />His lecture focused on how CD8 T cells adapt metabolically inside the tumor microenvironment. Because tumors are low in glucose, hypoxic, and full of suppressive signals, infiltrating T cells are forced to switch to mitochondrial metabolism to survive. Dr. Ho’s lab found that this adaptation comes with a cost: T cells accumulate damaged mitochondria, lose mitochondrial quality, and fail to clear the damage efficiently because autophagy/mitophagy is impaired.<br /><br />Using mouse and human T cells, his group showed that damaged mitochondria trigger accelerated degradation of mitochondrial proteins by the proteasome. This process releases “free” heme into the cytosol, where it acts as a signaling molecule. He demonstrated that elevated free heme promotes T cell exhaustion by disrupting the transcriptional regulator BACH2, shifting cells away from a stem-like, progenitor-exhausted state and toward terminal exhaustion. Mutating BACH2 so it cannot bind heme preserved T cell stemness and improved anti-tumor behavior.<br /><br />Finally, Dr. Ho connected these findings to therapy. In CAR T cells, lower proteasome activity correlated with better patient responses, and low-dose proteasome inhibition during CAR T-cell manufacturing helped preserve a less exhausted, more functional state. He concluded that targeting mitochondrial damage, proteasome activity, and heme signaling may improve cancer immunotherapy.

Keywords

Dr. Ping-Chi Ho

AAI BD Biosciences Investigator Award

tumor immunology

immunometabolism

CD8 T cells

tumor microenvironment

mitochondrial metabolism

T cell exhaustion

proteasome inhibition

CAR T cells