Tumor immunology

Edo Rezaprasga

Evidence for immune reactivity to

tumor
Tumor that have severe mononuclear
cell infiltration have a better prognosis
than those that lack it
Certain tumor regress spontaneously,
suggesting an immunological response
Some tumor metastases regress after
removal of primary tumor which reduce
the tumor load, thereby inducing the
immune system to kill residual tumor

Evidence for immune reactivity to

tumor
Increased incidence of malignancies in
immunodeficient patient
Aids patient are susceptible with Kaposi
sarcoma
Transplant patients are susceptible with EBV

Tumor-specific antibodies and T lymphocyte

have been observed in patient with tumor
The young and old population have
increased incidence of tumor. Those
member of population often have
decreased immune competency

Tumor associated antigens

Tumorigenesis may lead to
expression of new antigen or
alteration of existin antigen
2 main type of tumor antigens:
Tumor-specific transplantation antigen
(TSTA)
Tumor-associated transplantation
antigen (TATA)

Tumor specific transplantation

antigen
TSTA from chemical/UV/Virus-induced
neo antigen are often weakly
immunogenic / non-immunogenic
In most cases, TSTA cannot be identified
easily

Tumor associated transplantation

antigen
Tumor cells may express higher level
of TATA compared to normal cell
It can also be expressed during
development age and lost during adult
life, but reexpressed in tumor

Tumor associated developmental

antigens or onco-fetal antigen
Example: Alpha-fetoprotein (AFP) and
carcino-embryonic antigen (CEA)
AFP : 5x increase in hepatocellular
carcinoma
Used for monitoring hepatomas and
testicular cancer
Also increase during cirrhosis and other
forms of liver damage (but not as high as
cancer case)

CEA: 4-5x increase in colo-rectal cancer

May also increased in chronic cirrhosis,
pulmonary emphysema, and heavy smoking

Tumor associated transplantation

antigens on viral tumors
Virus are involved in some human
malignancies
Virus-induced tumor express cell
surface antigen which shared by all
tumor induced by the same virus
These antigens are characteristic of
tumor-inducing virus, regardless of
tissue origin or animal species where
the tumor exist

Tumor associated transplantation

antigens on viral tumors
DNA viruses
Papova (papilloma, polyoma) viruses:
Papilloma virus causes cervical cancer.
Hepatitis virus: Hepatitis B virus causes
hepatocellular cancer.
Adenoviruses may also be tumorigenic

RNA viruses
Retroviruses: Human T-lymphotropic
viruses (HTLV-I and HTLV-II) causes T cell
leukemias.

Immunity against tumor

Although there is enough evidence for antitumor immune reactivity in human, most of
the evidence are derived from malignancy
studies with animal
Mice were immunized by administering
irradiated tumor cells
These animals were found to be resistant to
rechallenge with the same live tumor

While antibodies may develop against few

cancer, cell-mediated immunity plays a critical
role in tumor rejection

Immunity against tumor

The Th cells recognize the tumor antigens that may
be shed from tumors and itll processes it to be
presented with class II MHC
These activated Th will produce cytokines, activating
B cells to produce antibody,
Secreting IFN-gamma which activate macrophages to
be tumoricidal
Provide help to cytotoxic tumor specific T cells
The cytotoxic tumor specific T cell recognize tumor
antigen and mediate tumor cell lysis
In tumor that exhibit decreased MHC antigen. NK cells
are also important in mediating tumor rejection

Escape from immunosurveillance

Tumor may not express neo-antigens
that are immunogenic
Fails to express co-stimulatory
molecules required to activate T cells
Certain tumors are known to lack or
poor expresser of MHC antigen
In early development of tumor, the
amount of antigen is too small to
stimulate the immune system

Escape from immunosurveillance

Rapid proliferation of cells, the
immune system is quickly
overwhelmed
Some tumors may evade the
immune system by secreting
immunosupressive molecules
Also, some tumor shed their antigens
which in turn may interact or block
antibodies and T cell to react with
tumor cells

References
1. Chabner BA, Lynch TJ, Longo DL.
Harrisons manual of oncology. 1st
ed. New York: McGraw-Hill Medical;
2008.
2. Tannock I, Hill R, Bristow R,
Harrington L. The basic science of
oncology. 5th ed London: McGrawHill Medical;2013
3. Ghaffar A, Nagarkatti M. Tumor
immunology. University of South