presentation source

Cancer & the Immune System 4/13/2015

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 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 4/13/2015

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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

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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 4/13/2015

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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- Hodgkin’s lymphoma Hodgkin’s disease

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Autologous Transplants – – – – – – – – – – –

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 45

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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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