Download Cancer Immunology

Cancer & the Immune System
5/1/2017
Hugh B. Fackrell
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Cancer & the Immune System
Assigned Reading
 Content Outline
 Performance Objectives
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– Key terms
– Key Concepts
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Short Answer Questions
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Assigned Reading
Janis Kuby’s Immunology 4th Ed
Chapter: 22 pp 539-561
 Janis Kuby’s Immunology 3rd Ed
 Chapter: 24 pp 573-596
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Content Outline
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Origins & Terms
Malignant Transformation
Tumours of the Immune System
Tumour Antigens
TATAs on human melanomas
Immune Response to Tumours
Tumour Evasion of Immune Response
Cancer Immunotherapy
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Origins & Terms
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Benign vs malignant
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Distribution of Cancer
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Diameter of Tumour (mm)
Growth of Breast Cancer
Death of Patient
Tumour first palpable
Tumour visible by X rays
1012cells
109cells
108cells
Tumour Cell doubling
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Altered Growth Properties
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Localized Benign Tumour
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Tumour Invasion of Basal
Lamina
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Metastasizes to Other Sites
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Tumour Antigens
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Tumour specific Antigens
– chemically induced
– virally induced
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Tumour associated antigens
– oncofetal tumour antigens
– oncogene proteins
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TSTA vs TATA
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Radio labelled anti CEA
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Genes
for TSTAs
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Malignant Transformation
Oncogenes
 Induction of cell proliferation
 Inhibition of cell proliferation
 Regulation of apoptosis
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Chromosomal translocations
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Tumour
Induction
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Induction of Tumours
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Tumours of the Immune
System
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TATAs on human melanomas
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TATAs on human melanomas
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Immunity to Polyoma virus(1)
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Immunity to Polyoma virus(2)
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Immunity to Polyoma virus (3)
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Immunity to Polyoma Virus (4)
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Immune Response to
Tumours
NK cells & macrophages
 Immune surveillance theory
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Tumour Evasion of Immune
Response
Immunologic enhancement
 Modulation of tumour antigens
 Reduce MHC-I
 No co-stimulatory signal
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Tumor Escape
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Cancer Immunotherapy
Modify Co-stimulatory signal
 Enhance APC activity
 Cytokine therapy
 MABs
 Tumour cell vaccines
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Cancers Treatable by Bone
Marrow Transplants
Allogenic/syngenic
Transplant
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Breast cancer
aplastic anemia
leukemia
ALL
CML
Myeolodysplasia
multiple myeloma
Non- Hodgkin’s lymphoma
Hodgkin’s disease
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Autologous Transplants
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Leukemia
AML
ALL
Multiple Myeloma
Non Hodgkin’s lymphoma
Hodkin’s disease
Solid tumours
Breast
ovarian
testicular
Neuroblastoma
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Transfect co stimulartory
signal
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Transfect with GM-CSF
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Lak cells & IL-2
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Mabs to B cell Lymphoma
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Tumour Cell Vaccine
Immune Response to MCA or PV
Transplant killed cells of
MCA induced sarcoma
A
 Challenge with
Sarcoma A- No Growth
 Challenge with
Sarcoma B- growth
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Transplant killed cells of
Polyoma Virus induced
sarcoma A
 Challenge with sarcoma
A no growth
 challenge with sarcoma
B no growth
 SV40 induced sarcoma
C- growth
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DONE!!!
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Performance Objectives
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Key Terms
antibody dependent cell mediated
cytotoxicity (ADCC), benign tumour,
cancer,
 carcinogens, proto oncogens, immune
surveillance, Specific immunotherapy,
 non specific immunotherapy,
immunotoxins,Lymphokine activated
killer cell(LAK),
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neoplasm, oncofetal antigens, oncogens,
tumour, tumour associated antigens,
 tumour associated transplantation
antigens, tumour specific antigens,
 tumour specific transplantation
antigens
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Key Concepts
Differentiate between a benign tumour and a
malignant tumour.
 Describe the concept of immunosurveillance
 Describe the different ways that tumours can
camouflage themselves to evade immune
defenses,
 Discuss the advantages of immunotherapy
over other forms of cancer therapy.
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Distinguish between specific and nonspecific
immunotherapy with the use of specific
examples.
 Describe immunotoxins.
 Describe the development of humanized
antibodies to tumour antigens
 Evalulate the contribution of T cells, NK cells,
Macrophages, and B cells to tumour
immunity.
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Distinguish between tumour specific
transplantation antigens and tumour
assoicated transplantation antigens.
 Describe oncofetal antigens.
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Short Answer Questions
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Explain how some cancer cells that can
make TGF-beta are immunosuppressive.
 Tumours and transplants are similar to one
another,yet very different. Explain this
observation in the context of what the
immune system recognizes and the result of
this recognition.
 The qualities of proliferation and
differentiation are essentially all that
distinguishes a normal cell from a cancer
cell. Explain.
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Design an experiment using mice that proves
that the immune system provides immunity
against tumours.
 Distinguish between tumour-specific
transplantation antigens (TSTA) and tumour
associated transplantation antigens (TATA).
 Design an experiment to show Tumour
associated Transplantation Antigens (TATA).
 What is the main difference separating cell
surface antigens from chemically induced and
virually induced cancers?
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Speculate on why this difference leads to
difficulty in designing anticancer vaccines.
 What are oncofetal antigens? Are they
important in tumour immunity? Why?
 What is immune surveillance?
 All evidence for immune surveillance is
indirect. Speculate on how you could get
direct evidence.
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What immune cells play a role in tumour
rejection? Briefly describe how each
accomplishes this task. Include such things as
cytokines, perforins, ADCC etc.
 Cancers camouflage themselves to evade
antitumour defenses. Pick three possible
forms of camouflage that you think are most
important, describe them and state why you
think they are most important.
 What are immunotoxins?
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Surgery, radiation and chemotherapy
are the methods most widely used to
treat cancer patients. What are the
problems with this regimen, and how
could immunotherapy overcome these
problems.
 Distinguish between specific and
nonspecific immunotherapy.
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