Immunopharmacogenomics combines the fields of immunogenomics and pharmacogenomics. While pharmacogenomics focuses on the influence of genomics on the variation of drug effect and adverse drug reactions (ADRs) within a population, immunogenomics focuses on the variation of immune-specific genes and their contribution towards immune-mediated diseases and immune-mediated ADRs. Thus, as a combination of two diverse yet advanced disciplines, immunopharmacogenomics is steadily emerging as a propellant in the development of immunotherapies.

The capability of high-throughput gene sequencing has transformed the realms of traditional genetic engineering. The rapid advancements in whole-genome sequencing empower us to probe into the molecular and genetic basis of a disease, and the mechanism and pathways involved. This gives us the supremacy in pinpointing the disease-associated genetic loci and thus studying a disease from a perspective that could only be dreamt of previously.

Of the promising prospects of immunopharmacogenomics, the development of targeted immuno-oncology remains a prominent one. Immunopharmacogenomics tools can enable the identification of T cell receptors that recognise cancer-specific neoantigens. The cytotoxic T cells also referred to as killer T cells are capable of destroying cancer cells. The capability of identifying these T cells allows the production of genetically engineered T cells that are more powerful in eliminating cancer cells. Additionally, immunopharmacogenomics offers insight into the molecular mechanism and pathways adopted in different immunotherapies. It helps in understanding how different immunotherapies function and modulate various immune checkpoint receptors in the treatment of cancer, along with the modifications that T cells undergo during immunotherapy.

In addition to immuno-oncology, Immunopharmacogenomics can have potential applications in autoimmune diseases. Tissue infiltrating lymphocytes (TILs) such as CD20+ B cells and CD8+ T cells have been associated with autoimmune diseases such as autoimmune thyroid diseases, Crohn’s disease, etc. Immunopharmacogenomics offers the possibility of characterising the TILs and other immune cells involved to improve the current understanding of the biomolecular pathway involved in the pathogenesis of autoimmune diseases.

Allergies such as food allergy are a condition closely associated with the immune system functioning that can manifest into a life-threatening situation. Interestingly, food allergies are unique in terms of their geographical prevalence. For example, peanut allergy, a well-known form of food allergy that affects a significant population in the U.S. every year, hardly affects people in Asian countries. Similarly, allergies specific to Asian countries such as Shellfish allergy, are only infrequently reported elsewhere. The T-cell receptors (TCRs) and B-cell receptors (BCRs) are crucial in inducing such immunogenic reactions. Immunopharmacogenomics can help in understanding the differential outcome of allergic reactions in different individuals in terms of the genomic build.

In adverse drug reactions (ADRs), immunopharmacogenomics through the screening of human leukocyte antigen (HLA) genes has created the scope of preventing immune-mediated ADRs that were only conceived as a possibility until now. While in organ transplant rejection, immunopharmacogenomics help in understanding the role played by cytotoxic T cells of the recipient in rejecting donor grafts, in addition to the factors that increase the possibility of rejection. This could help develop ways to manage and suppress the host immune response against transplants.

References

Karnes, J. H., Miller, M. A., White, K. D., et al. (2019). ‘Applications of Immunopharmacogenomics: Predicting, Preventing, and Understanding Immune-Mediated Adverse Drug Reactions’, Annu Rev Pharmacol Toxicol., 59: p.463–486. DOI: 10.1146/annurev-pharmtox-010818-021818

Nakamura, Y. (2015). ‘The Current and Future Applications of Immunopharmacogenomics’,Clinical Advances in Hematology & Oncology, 13(12), p.815-817.

Zewde, M., Kiyotani, K. Park, J.-H., et al. (2018). ‘The era of immunogenomics/immunopharmacogenomics’, J Hum Genet., 63, p.865–875. DOI: 10.1038/s10038-018-0468-1

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