Immunogenomics. Fundamentals, prospects in immuno-oncology and beyond

Rapid advancements in immunology as a subject have driven the need for creating sub-disciplines such as immunogenomics and immunopharmacogenomics. Our immune system comprising of the innate and adaptive systems is the key defence barrier against pathogens and nonself systems such as cancer. However, it can also mediate the development of various pathological conditions such as autoimmune diseases, adverse drug reactions, allergies, etc. The dual role of the immune system makes immunology a complex and challenging field of interest that only continues to grow.

Modern Immunogenomics focuses on precise whole-genome sequencing and sequence mapping of the human genome. The data collected from these activities help in identifying genetic loci and establish the genetic variation among individuals. This also helps in correlating the genetic variation that could serve as the differentiating factors between individuals displaying different immunogenic responses. It can also predict the disease resistance, disease progression, and response to therapeutics in individuals based on their genetic build. Thus immunogenomics can enlighten us with the knowledge of genetic and molecular pathways associated with diseases that were poorly understood to date, and ultimately assist in developing therapeutic strategies against them.

Modern concepts of immunogenomics emerged since the late 1980s, and have continued to develop by leaps and bounds. Immunogenomics-mediated advancements in immuno-oncology have been one of the greatest achievements in this era. Cancer is a life-threatening complex disease whose onset and progression are often linked to genetics. The complexity of the disease arises due to its difficulty in being treated due to the asymptomatic nature of certain cancers in the early stages which delays the diagnosis; and cancer metastasis.

The next-generation sequencing tools offered by immunogenomics, has helped us identify immune cell variants within the host, cancer cell mutations, predict the susceptibility towards cancer and other gene-linked diseases, and the development of personalised treatments. The discipline has allowed us to study the alterations that occur in the T-cell repertoire present within the tumour mass. Furthermore, immunogenomics methods can help to predict the neoantigens expressed by different types of cancers. Basically, the approach of immunogenomics in studying cancer relies on identifying genetic alterations in tumour cells that modify the amino acid sequences of the encoded proteins. It then evaluates the potential of these encoded proteins to function as neoantigens. These highly precise techniques not only allow identifying neoantigens unique to an individual patient, but also to different types of cancer. All this information is crucial in developing personalised vaccine and therapeutic strategies. Additionally, immunogenomic tools and methods being scalable have the potential scope of widespread clinical applications.

Another key application of immunogenomics is immune regeneration. With age, the immune system undergoes gradual deterioration such as exhaustion of memory cells, declining production of naïve lymphocytes, etc., a process known as immunosenescence. This makes the elderly population more susceptible to age-related disorders. Immunogenomics holds the promise of engineering and manipulating the immune system in elderly and immune-compromised individuals to restore its functionality. Albeit still in its infancy, the application of immunogenomics in regenerative therapy could be a magic boon to millions!

References

Liu, X. S., and Mardis, E. R. (2017). ‘Applications of Immunogenomics to Cancer’, Cell168(4), p.600–612. DOI: 10.1016/j.cell.2017.01.014

Miretti, M. M., and Beck, S. (2006). ‘Immunogenomics: molecular hide and seek’, Human genomics2(4), p.244–251. DOI:10.1186/1479-7364-2-4-244

Holt R. A. (2015). ‘Immunogenomics: a foundation for intelligent immune design’, Genome medicine7(1), p.116. DOI: 10.1186/s13073-015-0247-y

Chakraborty, S., and Rahman, T. (2012). ‘The difficulties in cancer treatment’, Ecancermedicalscience6(ed16). DOI: 10.3332/ecancer.2012.ed16

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