Tumor antigen

Oncofetal Antigens

Tumor antigen is an antigenic substance produced in

tumor cells, i.e., it triggers an immune response in the
host. Tumor antigens are useful tumor markers in identifying tumor cells with diagnostic tests and are potential
candidates for use in cancer therapy. The eld of cancer
immunology studies such topics.

Altered Cell Surface Glycolipids and Glycoproteins

Cell Type-Specic Dierentiation Antigens

2.1 Types

Mechanism of tumor antigenesis

Any protein produced in a tumor cell that has an abnormal

structure due to mutation can act as a tumor antigen. Such
abnormal proteins are produced due to mutation of the
concerned gene. Mutation of protooncogenes and tumor
suppressors which lead to abnormal protein production
are the cause of the tumor and thus such abnormal proteins are called tumor-specic antigens. Examples of
tumor-specic antigens include the abnormal products of
ras and p53 genes. In contrast, mutation of other genes
unrelated to the tumor formation may lead to synthesis
of abnormal proteins which are called tumor-associated
antigens.

Normal proteins in the body are not antigenic because of

self-tolerance, a process in which self-reacting cytotoxic
T lymphocytes (CTLs) and autoantibody-producing B
lymphocytes are culled centrally in primary lymphatic
tissue (BM) and peripherally in secondary lymphatic
tissue (mostly thymus for T-cells and spleen/lymph nodes
for B cells). Thus any protein that is not exposed to the
immune system triggers an immune response. This may
include normal proteins that are well sequestered from
the immune system, proteins that are normally produced
in extremely small quantities, proteins that are normally Other examples include tissue dierentiation antigens,
produced only in certain stages of development, or pro- mutant protein antigens, oncogenic viral antigens, cancerteins whose structure is modied due to mutation.
testis antigens and vascular or stromal specic antigens.
Tissue dierentiation antigens are those that are specic
to a certain type of tissue. Mutant protein antigens are
2 Classication of tumor antigens likely to be much more specic to cancer cells because
normal cells shouldn't contain these proteins. Normal
Initially tumor antigens were broadly classied into two cells will display the normal protein antigen on their MHC
categories based on their pattern of expression: Tumor- molecules, whereas cancer cells will display the mutant
Specic Antigens (TSA), which are present only on version. Some viral proteins are implicated in forming
tumor cells and not on any other cell and Tumor- cancer (oncogenesis), and some viral antigens are also
Associated Antigens (TAA), which are present on some cancer antigens. Cancer-testis antigens are antigens expressed primarily in the germ cells of the testes, but also
tumor cells and also some normal cells.
in fetal ovaries and the trophoblast. Some cancer cells
This classication, however,is imperfect because many aberrantly express these proteins and therefore present
antigens thought to be tumor-specic turned out to be ex- these antigens, allowing attack by T-cells specic to these
pressed on some normal cells as well. The modern clas- antigens. Example antigens of this type are CTAG1B and
sication of tumor antigens is based on their molecular MAGEA1.[1]
structure and source.
Proteins that are normally produced in very low quantities
Accordingly they can be classied as;
but whose production is dramatically increased in tumor
cells, trigger an immune response. An example of such
Products of Mutated Oncogenes and Tumor Sup- a protein is the enzyme tyrosinase, which is required for
pressor Genes
melanin production. Normally tyrosinase is produced in
minute quantities but its levels are very much elevated in
Products of Other Mutated Genes
melanoma cells.
Overexpressed or Aberrantly Expressed Cel- Oncofetal antigens are another important class of tulular Proteins
mor antigens. Examples are alphafetoprotein (AFP) and
Tumor Antigens Produced by Oncogenic carcinoembryonic antigen (CEA). These proteins are norViruses
mally produced in the early stages of embryonic devel1

opment and disappear by the time the immune system

is fully developed. Thus self-tolerance does not develop
against these antigens.
Abnormal proteins are also produced by cells infected
with oncoviruses, e.g. EBV and HPV. Cells infected
by these viruses contain latent viral DNA which is
transcribed and the resulting protein produces an immune
response.
In addition to proteins, other substances like cell surface
glycolipids and glycoproteins may also have an abnormal
structure in tumor cells and could thus be targets of the
immune system.

Importance of tumor antigens

Tumor antigens, because of their relative abundance in

tumor cells are useful in identifying specic tumor cells.
Certain tumors have certain tumor antigens in abundance.
Certain tumor antigens are thus used as tumor markers.
More importantly, tumor antigens can be used in cancer
therapy as tumor antigen vaccines.[2]

See also
Cancer immunotherapy

References

[1] Restifo, NP; Dudley, ME; Rosenberg, SA (Mar 22, 2012).

Adoptive immunotherapy for cancer: harnessing the T
cell response.. Nature reviews. Immunology 12 (4): 269
81. doi:10.1038/nri3191. PMID 22437939.
[2] M Hareuveni, C Gautier, M Kieny, D Wreschner, P
Chambon and R Lathe; Vaccination Against Tumor Cells
Expressing Breast Cancer Epithelial Tumor Antigen; Proceedings of the National Academy of Sciences, Vol 87,
9498-9502, 1990.

Kumar, Abbas, Fausto; Robbins and Cotran: Pathologic Basis of Disease; Elsevier, 7th ed.
Coulie PG, Hanagiri T, Takanoyama M: From Tumor Antigens to Immunotherapy. Int J Clin Oncol
6:163, 2001.

External links
Chapter on tumor antigens in Cancer Medicine at
NCBI

EXTERNAL LINKS

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