Cancer

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Cancer the Immune System

• Hugh B. Fackrell

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Cancer the Immune System

• Assigned Reading
• Content Outline
• Performance Objectives
• Key terms
• Key Concepts
• Short Answer Questions

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Assigned Reading

• Janis Kubys Immunology 4th Ed Chapter 22 pp
  539-561
• Janis Kubys Immunology 3rd Ed
• Chapter 24 pp 573-596

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Content Outline

• 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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Growth of Breast Cancer
Death of Patient
1012cells
Tumour first palpable
109cells
Tumour visible by X rays
108cells
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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

• Tumour specific Antigens
• chemically induced
• virally induced
• 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
• Breast cancer
• aplastic anemia
• leukemia
• ALL
• CML
• Myeolodysplasia
• multiple myeloma
• Non- Hodgkins lymphoma
• Hodgkins disease

• Autologous Transplants
• Leukemia
• AML
• ALL
• Multiple Myeloma
• Non Hodgkins lymphoma
• Hodkins 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 VaccineImmune Response to MCA or PV

• Transplant killed cells of MCA induced sarcoma A
• Challenge with Sarcoma A- No Growth
• Challenge with Sarcoma B- growth

• 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,Lymphokin
  e 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.