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1. Tumor
immunityA Seminar
Presented to,
Haematology Unit,
Federal Teaching Hospital, Abakaliki
Chukwu Paul Henry (BMLS. nig)
By

2. Outline• Introduction
• Aim and objectives
• Basic concepts of tumor immunity
• Tumor antigens
• Anti tumor effectors mechanisms
• Immunosurveillance and Immunoediting of cancer
• Laboratory investigation
• Cancer vaccine development Cancer immunotherapy
• Conclusion
• Recommendation
• References

3. Aim• To explain how the immune system of the host
responds to the presence of a tumor
Objectives
• To establish, the role of immunity in tumors, nay;
cancers
• To explain, the mechanism by which tumors evade the
immune system and harvest, the evidence for immune
reactivity to tumor
• To recognize, the changes in cellular characteristics due
to malignancy
• To re-evaluate, the host components which affect
tumor progression and implicate, the components
which protect it from the immune system

4. INTRODUCTION

5. INTRODUCTION
• Since the 1990s, tumor immunology has developed into a distinct discipline with a
metamorphosis from clinical observations in oncology to understanding its scientific
underpinnings (Srinivasan and Wolchok, 2004). The role of the immune system in Tumor
progression and response to therapy has become increasingly evident and appreciated over
the past decade (Enninga et al., 2015).
• Tumor recognition is a complex, challenging problem for the immune system, which must
distinguish proper cellular growth and organization from neoplastic transformation (Stewart
and Smith, 2011).
• Tumor immunogenicity varies greatly between cancers of the same type in different
individuals and between different types of cancer (Blankenstein et al., 2012).
• This work introduces some of the concepts required to understand the complex relationship
between the immune system and tumor development, and a selection of the complex
terminology which has characterized this field.
• The Three key points are:
• Tumor cells often do express new antigens ("neo-antigens") which are potential or actual
targets for immune recognition.
• Despite this fact, the immune system is often ineffective in eliminating tumors or preventing
their growth.
• Various means may be possible for modifying anti-tumor immune responses to render them
more effective, and to use immunological approaches for both diagnosis and treatment.

7. basic concepts of tumor immunity
neoplasia: Appearance of a tumor results from abnormal
proliferation of cells, through the loss or modification
of normal growth control (Jeeves, 2014).
Cancer: altered self-cells that have escaped normal
growth regulation mechanisms (Ohtani et al., 2007).
metastasis: spreading of cancerous cells via blood or
lymph to various tissues (Ohtani et al., 2007).

8. Metastasis
22.1

9. ORIGINS OF NEOPLASIA:
• CHEMICAL CARCINOGENS:
e.g., tobacco smoke and char-broiled steaks,
Methylcholanthrene
• IONIZING RADIATION:
X-rays, gamma rays and ultraviolet (UV) radiation
• VIRUSES: Many viruses carry their own oncogenes.
• (Jeeves, 2014).

10. EVIDENCE FOR IMMUNE REACTIVITY TO TUMORS
• Tumors that have severe mononuclear cell infiltration have a better
prognosis (Kawata et al., 1992; Ohtani et al., 2007).
• Certain tumors regress spontaneously (Challis and Stam, 1990; Nevala et al.,
2009; Hodi et al., 2010).
• Some tumor metastases regress after removal of primary tumor which
reduces the tumor load, thereby inducing the immune system to kill the
residual tumor (Lowe and Storkus, 2011).
• In 2007, Ohtani published a paper finding tumor infiltrating lymphocytes to
be quite significant in human colorectal cancer.
• The immune system may be able to mount an attack against the few tumor
cells that are spared by the chemotherapeutic agent (Marshall et al., 2006).
• There is an increased incidence of malignancies in immuno-deficient
patients (Jahr et al., 2001).
• Tumor-specific antibodies and T lymphocytes (detected in cytotoxicity and
proliferative response assays) have been observed in patients with tumors
(Odunsi and Old, 2007).
• The young and the old population have an increased incidence of tumors
(WHO, 2002).
• Hosts can be specifically immunized against various types of tumors (Dunn
et al., 2006).

11. Tumour
Induction
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12. Growth of Breast Cancer
DiameterofTumour(mm)
Tumour Cell doubling
Tumour visible by X rays
Tumour first palpable
Death of Patient
108cells
109cells
1012cells

13. Tumor antigens

14. (Zarour et al., 2003).
• Tumor suppressor genes
• Oncogenes
• Mutated normal genes
• Overproduction of proteins
• Glycolipids and proteins
• Fetal proteins
• Viruses
• Origin
• Cancer testes proteins
• (Mami-Chouaib et al., 2002; Hareuveni et
al., 1990 ).

15. Examples of
tumor
antigens-I
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bi

16. Examples of tumor antigens-II
Examples of tumor antigens 11
Immunobiology 6/e (Garland science,2005)

17. Importance of tumor antigens

18. Anti-tumor effectors mechanisms
Dr. Andrejs Liepins Science Photo Library

19. IMMUNOLOGICAL SURVEILLANCE:
• Paul Ehrlich
• Burnet and Thomas

20. The concept of Immunoediting
•– Elimination
•–Equilibrium
•– Escape
•(Ryungsa et al., 2007)

21. 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

22. Basic Tumor Immunosurveillance
Smyth, M. J. et al. Nature Immunology 2, 293 - 299 (2001)
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 the present tumor
antigens to CD8 and CD4
cells
3) subsequent T cytotoxic
destruction of the tumor
cells the occurs

23. MAC
MHC II
MHC I
APC
T
helper
cell
T
helper
2 cell
IL-2
B Cell Eosinophil
IL-4 IL-5
T helper
Memory
cell
T helper
Effectorc
ell
IL-1
T
cytotoxic
cell
T
cytotoxic
memory
cells
T cytotoxic
effector
cells
Perforins, apoptotic signals
Interferon
1
Cancer
Cell
T
cytotoxic
cell
Endogenous
antigen
Perforins, apoptotic signals
Generally
ineffective
tumor
surveillance,
but some
ADCC
Tumor
antigen or
tumor cell

24. TARGET CELL
MAC OR NK
Antibody-dependent cell-mediated cytotoxicity (ADCC)

25. NATURAL KILLER CELL
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. TUMOR ESCAPE MECHANISMS
T regulatory cells
Or kill them
Or T regulatory cells

27. FACTORS WHICH LIMIT ANTI-TUMOR IMMUNE RESPONSES
(IMMUNE ESCAPE)
 Tolerance
 Immunomodulation
 Immunoselection
 Enhancing antibodies
 Immunostimulation
 Blocking factors
 Immunosuppression
 (Dunn et al., 2004).

28. Tumor Immunodiagnosis
• The laboratory investigates the immune system and
ways to manipulate the immune response in distinct
but interrelated areas of investigations viz:
• 1. Detection of tumor associated antigens
– On tumor cells or in secretions
– Circulating in plasma
• 2. Immune competence of cancer patients
• 3. Immune response to tumor associated antigens
• Cell-mediated immunity
• Humoral
– Antibodies
– Blocking factor

29. • Carcinoembryonic antigen (CEA) is a protein-polysaccharide complex present in colon
carcinomas and in normal fetal intestine, pancreas, and liver.
• α-Fetoprotein, a normal product of fetal liver cells, is also present in the sera of patients
with primary hepatoma, nonseminomatous germ cell tumors, and, frequently, ovarian or
testicular embryonal carcinoma.
• β Subunit of human chorionic gonadotropin (β-hCG), measured by immunoassay, is the
major clinical marker in women with gestational trophoblastic neoplasia (GTN
• Prostate-specific antigen (PSA), a glycoprotein located in ductal epithelial cells of the
prostate gland,
• CA 125 is clinically useful for screening, diagnosing, and monitoring therapy for ovarian
cancer,
• β 2 -Microglobulin is often elevated in multiple myeloma and in some lymphomas. Its
primary use is in prognosis.
• CA 19-9 was originally developed to detect colorectal cancer but proved more sensitive for
pancreatic cancer
• CA 15-3 and CA 27-29 are elevated in most patients with metastatic breast cancer.
• Chromogranin A is used as a marker for carcinoid and other neuroendocrine tumors.
• Thyroglobulin is produced by the thyroid and may be elevated with various thyroid
disorders.
• TA-90 is a highly immunogenic subunit of a urinary tumor–associated antigen.

30. Immunotherapy of Cancer
• Passive Cellular Immunotherapy
• Lymphokine-activated killer (LAK) cells
• Tumor-infiltrating lymphocytes (TILs
• Passive Humoral Immunotherapy
• Active Specific Immunotherapy
• Peptide-based vaccines use peptides from defined TAAs.
• DNA vaccines
• Autochthonous tumor cells (cells taken from the host)
• Allogeneic tumor cells (cells taken from other patients)
• Nonspecific Immunotherapy
• Interferons (IFN-α, -β, -γ)
• Certain bacterial adjuvants (BCG and derivatives, killed
suspensions of Corynebacterium parvum) have tumoricidal
properties..

31. Conclusion
• It can be harvested through this research work that:
• Normal cells can be transformed in vitro by chemical and physical carcinogens, or by
transforming viruses. They typically express tumor specific antigens on their cell surface.
• Immune responses to tumors include: CTL mediated cell lysis, NK cell killing, ADCC and
macrophage mediated cell killing. There are several cytotoxic factors such as TNF‐alpha and
TNF‐β.
• Some tumors cells utilize immune response evading mechanisms.
• There are new strategies for cancer immune therapy: identification of specific tumor
antigens, effective presentation of tumor antigens, generation of activated CTLs and T helper
cells.
• Chronic inflammation in the promotion of tumorigenesis is well established, and cancer-
associated tolerance/immune evasion has long been appreciated.
• Recent development of immunotherapies targeting cancer associated inflammation and
immune tolerance such as cancer vaccine, cell therapies, neutralizing antibodies, and
immune checkpoint inhibitors, have shown promising clinical results.

32. Recommendations
• Having re-evaluated, harvested, and produced evidence based hybrid
factual information on tumor immunity with apparent precision and
indefatigable poke into the nitty-gritty of this topic, I hereby recommend:
• That adequate and prompt diagnosis of tumor is made available since early
diagnoses can lead to good management or even cure.
• That public enlightenment and awareness campaign is put in place to avert
root causes of cancers including chemicals, exposure to radiation, viral
infection and other oncogenically potential substances.
• Young and vibrant scholars should be encouraged to be actively involved in
cancer research programs in order to produce more evidence based facts
towards the elimination of this killer omen.
• Meanwhile, since good and adequate meal formula can boost our immune
system, let us eat and always be full in God’s discipline.
• Finally, Government should play active role in improving further research
and recommendations, since treatments are always very toxic, and the
financial burden of novel therapies is significant.

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38. Thank you for listening
Thank you for listening