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Pharmacogenomics traditionally examines how inherited genetic variations influence drug metabolism, pharmacodynamics, and toxicity. Recent advances have highlighted the immune system as a critical determinant of therapeutic efficacy and safety. Immunopharmacogenomics integrates genetic information—particularly HLA polymorphisms—with the dynamic properties of T-cell and B-cell receptor (TCR and BCR) repertoires to explain interindividual differences in drug responses and immune-related toxicities or diseases. I introduce how HLA diversity, immune repertoire heterogeneity, and immune-tolerance mechanisms shape therapeutic outcomes across diverse clinical contexts, including immune-mediated adverse drug reactions, cancer immunotherapy, graft-versus-host disease, autoimmune disorders, food allergy, transplantation, and vaccination. Emerging evidence indicates that immune-repertoire sequencing captures dynamic clonal shifts and diversity changes associated with disease states and treatment responses, providing both mechanistic insights and predictive biomarkers. By integrating genetic data with immune-repertoire analyses, immunopharmacogenomics establishes a foundation for individualized risk prediction, safer drug design, and more precise immunotherapies—including neoantigen-based treatments, TCR-engineered T-cell therapy, and bispecific antibodies—thereby advancing the next phase of precision medicine for cancer and autoimmune diseases.