- Cancer remains a leading cause of death globally, with an estimated 12.7 million cases expected to increase to 21 million by 2030. - Tumors can be detected through abnormal cell proliferation caused by genetic mutations or loss of growth control. - The immune system responds to tumor antigens expressed by cancer cells and tumor-associated antigens shared between tumors induced by the same virus. - However, tumors have developed multiple mechanisms to evade immune surveillance such as low immunogenicity, antigen modulation, immune suppression, and inducing lymphocyte apoptosis.

1. Tumor immunology
-tumor antigen, response to tumor and evasion
of the immune system, cancer immunotherapy,
stem cell therapy

2. “swelling”) results from ABNORMAL
PROLIFERATION of cells, through the loss or
•Cancer remains one of the leading causes of death
globally, with an estimated 12.7 million cases around the
world affecting both sexes equally. This number is
expected to increase to 21 million by 2030.
•Appearance of a tumor (from the Latin word for
modification of normal growth control.
•Cells which normally do not divide (e.g. muscle or
kidney cells) may start proliferating, or cells which
normally do proliferate (e.g. basal epithelial cells or
hemopoeitic cells) may begin dividing in an uncontrolled
fashion.
Cancer

3. Carcinogens
•Radiation: Ultraviolet light, sunshine; X-rays,
radioactive elements induce DNA damage and
chromosome breaks.
•Chemical: smoke and tar, countless chemicals that
damage DNA (mutagens).
•Oncogenic viruses: insert DNA or cDNA copies of viral
oncogens into the genome of host target cells.
• Hereditary: certain oncogenes are inheritable.

4. Classification of cancer
•Carcinomas: epithelial origin involving the skin,
mucous membranes, epithelial cells in glands
•Sarcomas: cancer of connective tissue.
•Lymphomas: T- B-cell, Hodgkin’s, Burkitt’s lymhomas;
- solid tumors
•Leukemias: disseminated tumors - may be lymphoid,
myeloid, acute and chronic.

5. TumorImmunology
•Tumor antigens
•Effectors mechanisms in anti-tumor immunity
•Mechanisms of tumor evasion of the Immune system
•Immunotherapy for tumors

6. TumorAntigen
•Many tumors can be shown to express cell
surface antigens which are not expressed in the
normal progenitor cells before the neoplastic
transformation event.
•These antigens have been categorized based on
their nature and distribution, resulting in a
complex collection of acronyms, some of which
are defined as:

7. TumorAntigen
1. Tumor-Specific TransplantationAntigens, or TSTA
Chemical or radiation-induced tumors each generally
express a unique neo-antigen, different from other
tumors induced by the same or different agent.
2. Tumor-Associated TransplantationAntigens, or
TATA
Tumors induced by the same virus express antigens
shared between different tumors. These consist of
membrane-expressed virally encoded antigens, and have
been termed Tumor-Associated TransplantationAntigens
(since they are not, strictly speaking, tumor “specific”).

8. TumorAntigen
3. Oncofetal antigens:
•These are TATAs which are more or less selectively
expressed on tumors, but are also shared with some
normal fetal or embryonic tissues.
•Examples include carcinoembryonic antigen (CEA,
shared with healthy fetal gut tissue), and alpha-
fetoprotein (AFP, also present in the serum of healthy
infants, but decreasing by one year of age).

9. Tumorsstimulateanimmuneresponse
•Animals can be immunized against tumors
•Immunity is transferable from immune to naïve animals
•Tumor specific antibodies and cell have been detected in
humans with some malignancies

10. proto-oncogenes
tumor
suppressor
genes
oncogenes
carcinogen
results in mutation
dysfunctional
tumor suppressor
genes
inherited
defect
increased GF
increased GF receptors
exaggerated response to GF
loss of ability to
repair damaged
cells or induce
apoptosis

11. Fourmechanismsof oncogene activityto deregulate cell division

12. ⦿ Escape normal intercellular communication
⦿Allow for rapid growth
⦿ Increased mobility of cells
⦿Invade tissues
⦿Metastasis
⦿Evade the immune system
12

13. EXPERIMENTALEVIDENCEFORTUMORANTIGENSANDIMMUNE
RESPONSE

14. Immunosurveillance
•An hypothesis that states that a physiologic function of
the immune system is to recognize and destroy
malignantly transformed cells before they grow into
tumors.
•Implies that cells of the immune system recognize
something “foreign” on transformed/tumor cells.

15. Immune Surveillance of Tumors
Normal cell
Transformed (cancerous) but also antigenic
Mutation or virus
Transformed (cancerous) but
escapes from immune response
Immune
response
Dead
Mutation
Analogous to a bacterial population being treated with antibiotics
such that antibiotics resistant mutants take over the population

16. ⦿Macrophage/Dendritic cell attack or
antigen presentation
⦿CD8 cell-mediated cytotoxicity
⦿Antibody dependent cell mediated
cytotoxicity (ADCC)
⦿Natural killer cells

17. Tumors canbothactivateandsuppressimmunity
Tumors can activate the immune response (ex.
expression of foreign antigen with MHCI) or
suppress the immune response (activation of T
regulatory cells that release IL-10 and TGF) – the
balance determines whether the cancer becomes
clinically relevant or not.

18. Basic TumorImmunosurveillance
1) The presence of tumor cells and tumor antigens
initiates the release of “danger” cytokines such as
IFN and heat shock proteins (HSP).
2) These cause the activation and maturation of
dendritic cells such that they present tumor antigens
to CD8 and CD4 cells
3) subsequent T cytotoxic destruction of the tumor
cells occurs

19. Helper T cells
CD4+ T cells: reacting to class II MHC peptide
complex, they secret cytokines.
cytotoxic T cell response (Th1 helper T cells)
antibody response (Th2 helper T cells)
Dendritic Cells
The professional antigen-presenting cells In the final
common pathway for activating naïveTcells.

20. A
C
MHC II
M
MAC
T
helper
cell
IL-2
T
helper
Memor
y cell
T
helper
effector
cell
IL-1
Interferon
Macrophages and dendritic cells
can directly attack tumor cells,
or more commonly can express
exogenous antigens (TSA’s or
bits of killed tumor cells) to
CD4 cells
Tumor cell
or tumor
derived
antigen
Dendritic and Macrophage
Presentation of Tumor
Antigen to CD4 Cells

21. Cytotoxic T cells (CTLs)T cells(CTLs)
CD8+ T cells: attaching to class I MHC peptide
complex, they destroy cancer cells by perforating
the membrane with enzymes or by triggering an
apoptotic pathway.

22. 22
MAC or
B cell
(APC)
MHC 1
T
cytotoxic
cell
Perforins, apoptotic signals
Exogenous
antigen
T
cytotoxi
c
memory
cells
T
cytotoxic
effector
cells
T
Cytotoxic
Cell
Activity in
Tumor
Surveillanc
e
Cancer
Cell
T
cytotoxic
cell
Endogenous
antigen

23. Cytokines
•Regulating the innate immune system: NK cells, macrophages
and neutrophils; and the adaptive immune system: T and B cells
•IFN- α-- upregulating MHC class I tumor antigens and adhesion
molecules; promoting activity of B and T cells, macrophages, and
dendritic cells.
•IL-2-- T cell growth factor that binds to a specific tripartite
receptor on T cells.
•IL- 12– promoting NK and T cell activity and a growth factor
for B cells
•GM-CSF(Granulocyte-monocyte colony stimuating factor) --
reconstituting antigen-presenting cells

24. Antibody- producedbyB cells
•Direct attack: blocking growth factor receptors, arresting
proliferation of tumor cells, or inducing apoptosis.
-- is not usually sufficient to completely protect the body.
• Indirect attack: -- major protective efforts
(1) ADCC(antibody-dependent cell mediated cytotoxicity)
-- recruiting cells that have cytotoxicity, such as monocytes and
macrophages.
(2) CDC (complement dependent cytotoxicity)
-- binding to receptor, initiating the complement system,
'complement cascade’, resulting in a membrane attack
complex causing cell lysis and death.

25. NK
Target cell (infected or
cancerous)
Perforin and enzymes
killer activating receptor
Do not recognize tumor cell via antigen specific
cell surface receptor, but rather through
receptors that recognize loss of expression of
MHC I molecules, therefore detect “missing
self” common in cancer.

26. ⦿Low immunogenicity
⦿Antigen modulation
⦿Immune suppression by tumor cells or T
regulatory cells
⦿Induction of lymphocyte apoptosis

27. Defects in mechanisms of MHCI
production can render cancer cells
“invisible” to CD8 cells

28. Tumors can escape immunity(andimmunotherapy) by selecting for resistant clones
that have occurreddue to geneticinstability

29. Elimination refers to
effective immune
surveillance for clones
that express TSA
Equilibrium
refers to the
selection for
resistant
clones (red)
Escape refers to the
rapid proliferation of
resistant clones in the
immunocompetent
host
29

30. 1 2
Avoidance of tumor surveillancethroughrelease of immune
suppressants

31. Tumor cells induceapoptosis in T lymphocytes via FAS activation
1)Cancer cells express FAS ligand.
2)Bind to FAS receptor on T lymphocytes leading
to apoptosis.

32. Cancer Immunotherapy
• Immunotherapy is the most recent advanced
technique in cancer therapy.
• Cancer Immunotherapy is the use of immune system
to reject Cancer. The main purpose of this premise is
stimulating the patient’s immune system to attack the
malignant tumour cells that are responsible for the
disease.
• Immunotherapy works to harness the innate powers of
the immune system to fight cancer.
• It fights cancer more powerfully, to offer long-term
protection, with less side effects.
• It may hold greater potential than current treatments,
due to unique properties of Immune System.

33. MonoclonalAntibodies
Cytokines
Adoptive cell Therapy
Cancer Vaccines

34. Thank you