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UNIVERSITY OF CAPE COAST

COLLEGE OF HEALTH AND ALLIED SCIENCES


SCHOOL OF ALLIED HEALTH SCIENCE
DEPARTMENT OF BIOMEDICAL SCIENCES

COURSE TITLE: APPLIED IMMUNOLOGY


COURSE CODE: BMD 312
INDEX NUMBER: AH/BMS/21/0001

LECTURER’S NAME: REV. DR. BENJAMIN AMOANI


DATE OF SUBMISSION: 25TH JUNE, 2024
1. Identify the various specialized mechanisms used by tumor cells for evading host immune
responses.

Tumor cells develop a number of mechanisms to evade the immune system, allowing them to
grow and spread. Here are some of the most common mechanisms:

1. Recruitment of immunosuppressive cells: Tumor cells can recruit immunosuppressive


cells, such as myeloid-derived suppressor cells and regulatory T cells, to the tumor
microenvironment. These cells can suppress the immune response and promote tumor
growth. Example DKK1, or Dickkopf-1, promotes tumor immune evasion by
manipulating macrophages, a type of immune cell. DKK1 reprograms macrophages into
immunosuppressive tumor-associated macrophages (TAMs) that suppress the anti-tumor
activity of immune cells like CD8+ T cells and natural killer (NK) cells. This creates an
immunosuppressive tumor microenvironment that allows tumors to grow and spread.
2. Downregulation of MHC molecules: MHC molecules are cell-surface proteins that
present antigens (foreign substances) to immune cells. Tumor cells can downregulate
MHC molecules, making it difficult for immune cells to recognize and attack them.
3. Immune checkpoint inhibition: Immune checkpoints are molecules that normally help
regulate the immune response. Tumor cells can express ligands that bind to immune
checkpoint receptors on T cells, preventing them from killing tumor cells.
4. Production of immunosuppressive factors: Tumor cells can produce a variety of
factors that suppress the immune response, such as cytokines and enzymes. These factors
can inhibit the activity of immune cells or promote the growth of regulatory T cells,
which suppress immune responses.
5. Disguise as healthy cells: Tumor cells can disguise themselves as healthy cells by
mimicking their surface molecules. This can make it difficult for the immune system to
recognize and attack them.

2. Enumerate the various biochemical and molecular genetic approaches have been used to
identify tumor antigens.

Biochemical and molecular genetic approaches have revolutionized the identification of tumor
antigens, paving the way for the development of targeted cancer immunotherapies. Here are
some key methods employed in this endeavor:

1. Serial antigenic cloning (SAC): This technique involves isolating tumor cells and
creating protein extracts. These extracts are then injected into animals to elicit an immune
response, and the antibodies produced by the animals are used to identify tumor-specific
antigens through protein separation techniques like chromatography.
2. Cytotoxic T lymphocyte (CTL) cloning: This method isolates T cells from tumor
patients that can recognize and kill tumor cells. The genes encoding the antigens
recognized by these T cells are then identified using molecular biology techniques.
3. Expression cloning: Tumor cDNA libraries are introduced into host cells, and these cells
are screened for their ability to be recognized and lysed by CTLs. This allows researchers
to pinpoint the genes encoding tumor antigens.
4. MHC peptide elution: This approach involves isolating MHC molecules (proteins that
present antigens to T cells) from tumor cells. The peptides bound to these MHC
molecules are then eluted and analyzed using mass spectrometry to identify tumor-
derived antigens.
5. Next-generation sequencing (NGS): This powerful technology allows researchers to
sequence the entire genome or transcriptome of tumor cells and identify mutations or
alterations in gene expression that could potentially encode tumor antigens.

Reference

1. Gubin, M. M., Zhang, X., Schuster, H., Caron, E., Ward, J. P., Noguchi, T., ... &
Schreiber, R. D. (2014). Checkpoint blockade cancer immunotherapy targets tumour-
specific mutant antigens. Nature, 515(7528), 577-581.
https://doi.org/10.1038/nature13988
2. Hacohen, N., Fritsch, E. F., Carter, T. A., Lander, E. S., & Wu, C. J. (2013). Getting
personal with neoantigen-based therapeutic cancer vaccines. Cancer Immunology
Research, 1(1), 11-15.
3. Liu, X. S., Mardis, E. R. (2017). Applications of Immunogenomics to Cancer. Cell,
168(4), 600-612. https://doi.org/10.1016/j.cell.2016.11.043
4. Ott, P. A., Hu, Z., Keskin, D. B., Shukla, S. A., Sun, J., Bozym, D. J., ... & Wu, C. J.
(2017). An immunogenic personal neoantigen vaccine for patients with melanoma.
Nature, 547(7662), 217-221

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