3. • Tumor immunology is mainly to study the
immunogenicity of tumor and the mechanism of
immune response to tumor, to demonstrate the
relationship between the status of immune system
and the generation, development of tumor, to
explore the method of tumor diagnosis, therapy
and prevention.
. Immunosurveillance
IntroductionIntroduction
4.
CANCER: ORIGIN AND
TERMINOLOGY
• In most organs and tissues of a mature animal, a
balance is usually maintained between cell
renewal and cell death. The various types of
mature cells in the body have a given life span; as
these cells die, new cells are generated by the
proliferation and differentiation of various types
of stem cells
5. Malignant Transformation of Cells
Induction of malignant transformation with chemical or Physical
carcinogens appears to involve multiple steps and at least two distinct
phases: initiation and promotion. Initiation involves changes in the
genome but does not, in itself, lead to malignant transformation. After
initiation, promoters stimulate cell division and lead to malignant
transformation.
6. ONCOGENES AND CANCER INDUCTION
In 1971, Howard Temin suggested that
oncogenes might not be unique to
transforming viruses but might also be
found in normal cells; indeed, he
proposed that a virus might acquire
oncogenes from the genome of an
infected cell
He called these cellular genes proto-
oncogenes, or cellular oncogenes (c-
onc), to distinguish them from their
viral counterparts (v-onc)
In the mid-1970s, J. M. Bishop and H. E. Varmus identified a DNA
sequence in normal chicken cells that is homologous to v-src from Rous
sarcoma virus. This cellular oncogene was designated c-src. Since these
early discoveries, numerous cellular oncogenes have been identified.
7. Proto-Oncogenes Can Be Converted to
Oncogenes
In 1972, R. J. Huebner and G. J. Todaro
suggested that mutations or genetic
rearrangements of proto-oncogenes by
car-cinogens or viruses might alter the
normally regulated function of these
genes, converting them into potent
cancer-causing oncogenes.
some malignantly transformed cells
contain multiple copies of cellular
oncogenes, resulting in increased
production of onco-gene products.
8. Tumors of the Immune System
Tumors of the immune system are
classified as lymphomas or leukemias.
Lymphomas proliferate as solid tumors
within a lymphoid tissue such as the bone
marrow, lymph nodes, or thymus; they
include Hodgkin’s and non-Hodgkin’s
lym-phomas. Leukemias tend to
proliferate as single cells and are detected
by increased cell numbers in the blood or
lymph. Leukemia can develop in lymphoid
or myeloid lineages
9. TUMOR ANTIGENS
The subdiscipline of tumor immunology
involves the study of antigens on tumor
cells and the immune response to these
antigens. Two types of tumor antigens
have been identified on tumor cells:
tumor-specific transplantation antigens
(TSTAs)&tumor-associated
transplantation antigens (TATAs)
Antigens encoded by genes exclusively
expressed by tumors
Antigens encoded by variant forms of
normal genes that have been altered by
mutation
10. SOME ANTIGENS ARE TUMOR-SPECIFIC
Tumor-specific antigens have been
identified on tumors induced with
chemical or physical carcinogens and on
some virally induced tumors.
Demonstrating the presence of tumor-
specific antigens on spontaneously
occurring tumors is particularly difficult
because the immune response to such
tumors eliminates all of the tumor cells
bearing sufficient numbers of the antigens
and in this way selects for cells bear-ing
low levels of the antigens
11. Tumor Antigens May Be Induced
by Viruses
In contrast to chemically induced
tumors, virally induced tumors express
tumor antigens shared by all tumors
induced by the same virus. For
example, when syngeneic mice are
injected with killed cells from a
particular polyoma-induced tumor, the
recipients are protected against
subsequent challenge with live cells
from any polyoma-induced tumors.
12. SCHIMATIC REPRESENTATION OF
THE ANTI –TUMOR IMMUNE
RESPONSE
Following the discovery that antibodies
could be produced to tumor-specific
antigens, attempts were made to protect
animals against tumor growth by active
immunization with tumor antigens or
by passive immunization with
antitumor antibodies. Much to the
surprise of the researchers, these
immunizations did not protect against
tumor growth; in many cases, they
actually enhanced growth of the tumor
13. Antibodies Can Modulate Tumor
Antigens
Certain tumor-specific antigens have
been observed to disappear from the
surface of tumor cells in the presence
of serum antibody and then to reappear
after the antibody is no longer present
This phenomenon, called antigenic
modulation, is readily observed when
leukemic T cells are injected into mice
previously immunized with a leukemic T-
cell anti-gen (TL antigen). These mice
develop high titers of anti-TL antibody,
which binds to the TL antigen on the
leukemic cells and induces capping,
endocytosis , and/or shedding of the
antigen-antibody complex.
15. ENHANCEMENT OF APC ACTIVITY CAN
MODULATE TUMOR IMMUNITY
Use of transfected tumor cells for cancer im-munotherapy. (a) Tumor cells
transfected with the B7 gene express the co-stimulatory B7 molecule, enabling
them to provide both acti-vating signal (1) and co-stimulatory signal (2) to CTL-Ps.
As a result of the combined signals, the CTL-Ps differentiate into effector CTLs,
which can mediate tumor destruction. In effect, the transfected tu-mor cell acts
as an antigen-presenting cell. (b) Transfection of tumor cells with the gene encoding
GM-CSF allows the tumor cells to se-crete high levels of GM-CSF. This cytokine will
activate dendritic cells in the vicinity of the tumor, enabling the dendritic cells to
present tu-mor antigens to both TH cells and CTL-Ps.
16. CYTOKINE THERAPY CAN AUGMENT
IMMUNE RESPONSES TO TUMORS
The isolation and cloning of the various
cytokine genes has facilitated their large-scale
production. A variety of experimental and
clinical approaches have been developed to use
recombinant cytokines, either singly or in
combination, to augment the immune response
against cancer. Among the cytokines that have
been evaluated in cancer immunotherapy are
IFN- , , and ; IL-1, IL-2, IL-4, IL-5, and IL-12;
GM-CSF; and TNF. Although these trials have
produced occasional encouraging results, many
obstacles remain to the successful use of this
type of cancer immunotherapy.
17. IN VITRO–ACTIVATED LAK AND
TIL CELLS
Photomicrographs of cultured normal
melanocytes (top) and cultured cancerous
melanoma cells (bottom) in the presence (left)
and absence (right) of tumor necrosis factor
(TNF- ). Note that, in the presence of TNF- ,
the cancer cells stop proliferating whereas
TNF- has no inhibitory effect on proliferation
of the normal cells.
Animal studies have shown that
lymphocytes can be activated against
tumor antigens in vitro by culturing
them with x-irradiated tumor cells in
the presence of IL-2 and added tumor
antigens. These activated lymphocytes
mediate more effective tumor
destruction than untreated lymphocytes
when they are re injected into the
original tumor-bearing animal.
18. CONCLUSION
Tumor cells differ from normal cells in numerous ways. In particular,
changes in the regulation of growth of tumor cells allow them to proliferate
indefinitely, then invade the underlying tissue, and eventually metastasize to
other tissues. Normal cells can be transformed in vitro by chemical and
physical carcinogens and by transforming viruses. Transformed cells exhibit
altered growth properties and are sometimes capable of inducing cancer
when they are injected into animals.
The use of a variety of genetic, biochemical, and immunological
approaches has allowed the identification of several tumor-associated
antigens In many cases the antigen is expressed on more than one type of
tumor.
19. Reference:
Kuby by immunology 6th
edition
Paradoll .D.M 1996 cancer vaccines a road map for
the next decade.curr.opin.immunology
http://www.oncalink.upenn.edu/
http://www.cancer.org/index_4up.html
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