pharmacogenomics

1. PHARMACOGENOMICS
AND THE IMMUNE
SYSTEM
Presented by: Fatima tu Zahra
Presented to: Sir Hafiz Bilal

2. PHARMACOGENOMICS

4.  What is
immunopharmacogenomics?
 Immunopharmacogenomics
incorporates 2 study areas:
immunogenomics and
pharmacogenomics.
 This field relies on next-generation
sequencing of T-cell and B-cell
receptors to identify the molecular
mechanisms that underlie various
disease states and drug responses.
 How can
immunopharmacogenomics be used
in hematologic and oncologic
disorders?
 Immunopharmacogenomic analysis
can identify the T cells that are able to
kill cancer cells.
 This field of study could be used to
predict how a patient will respond to
anticancer treatment

5. IMMUNOGENOMICS IS AN
INFORMATION SCIENCE
 Adaptive immune system is the biggest source of human genetic
variation
 Each of us carries four to five million single nucleotide polymorphisms
 With advancing technology, we continue to build on the hard work and
remarkable insights that established the fundamental principles and
mechanistic underpinnings of the immune system, such as somatic
recombination, clonal selection and self-tolerance

6.  How can the immune microenvironment
predict response to treatment?
 Various aspects of the immune
microenvironment can predict how a patient
will respond to immunotherapy.
 The number of somatic mutations correlates to
outcome with immune checkpoint antibodies.
 It is now possible to characterize millions of T-
cell receptors with a single test.
 Progress in DNA sequencing technology has
allowed us to obtain the
variable/diversity/joining (V[D]J) combination
as well as the inserted/deleted nucleotides
during the recombination process of the T-cell
receptor β chain.
 What are some of the complexities of the
human immune system?
 The T-cell and B-cell repertoires are
enormously different in each person because
of variations in the HLA types that present
antigens to T cells.
 T cells are divided into 2 classes by the T-cell
receptors: the α/β T-cell receptor and the γ/δ
T-cell receptor.
 During the differentiation of lymphocytes,
genes for the T-cell and B-cell receptors
undergo a process known as recombination to
generate receptors.
 Cancer has many somatic mutations, some of
which generate certain amino acid changes.
The amino acid change can create cancer-
specific antigens on the cell surface.

7. WHAT DO WE HOPE TO DISCOVER?
 An effort to provide, in particular, a more comprehensive view of B-cell
receptor (BCR) alleles will greatly facilitate the interpretation of antibody
repertoire data, and will in turn facilitate therapeutic antibody
development, by making allelic variants more readily distinguishable
from somatic hypermutations.
 In isolation a given T cell can be shown to interact selectively with a
major histocompatibility complex (MHC) presenting one peptide but not
another, but the ‘one T cell–one antigen’ view articulated in early
formulations of the clonal selection theory has been thoroughly refuted
on a theoretical basis.

8.  What are some other potential
applications of
immunopharmacogenomics?
 Immunopharmacogenomics will be
important not only in oncology but also
in autoimmune diseases.
 Immunopharmacogenomics can be
used to predict the risk of graft-vs-host
disease after bone marrow
transplantation.
 It should also be important for food
allergies.
 What are the challenges involved
with the application of
immunopharmacogenomics in
clinical practice?
 Because of the high complexity and
variability seen in HLAs, antigens, the
T-cell repertoire, and the B-cell receptor
repertoire, it will be necessary to
accumulate a huge amount of data.

9. APPLYING WHAT WE LEARN
 Approaching immunogenomics as information science, in pursuit of an
increasingly comprehensive view of connectivity within the immune
system at rest and under challenge, is likely to lead to new and better
strategies for immune intervention.
 At the current stage of the global COVID-19 pandemic, many vaccine
trials and programs are underway worldwide, offering opportunities to
investigate the role of genetic factors in vaccine-mediated immune
responses.