肿瘤免疫简介

Immune surveillance of tumors-II
Identification of tumor Ags by CTLs
Examples of tumor antigensI
Examples of tumor antigens-II
Tumor antigens arise by point mutations in self proteins
(1)
(2) Immunosurveillance and immunoediting of cancer (3) Mechanisms of immune evasion by tumors (4) Cancer vaccine development Cancer immunotherapy (5) Inflammation & Cancer, and other topics
2. Innate immune responses to tumors:
Overview of Tumor Immunology
1. Tumorigenesis
2. Discovery of the protective immune response against tumors. 3. T cells recognize specific antigens on tumors
Immune responses to tumors
1. Adaptive immune responses to tumors:
a. CD8 CTLs are the key players on the killing effect of tumors. b. CD4 T helper cells => cytokines => CTLs c. Abs => activating complements or Ab-dep cell-med toxicity => preventing oncogenic viruses a. NK cells kill many types of tumor cells that have reduced class-I but express ligands for activating NK cells. b. Macrophages => Ab-med phagocytosis => Cytokines (TNF-a), ROS, & NO
Evaluation
1. Attendance – 60% 2. Paper & Project Presentation – 20 %
3. Class performance – 20%
Overview of Tumor Immunology
1. Tumorigenesis
2. Discovery of the protective immune response against tumors. 3. T cells recognize specific antigens on tumors 4. Tumors can escape in many ways 5. Immunotherapy for tumors
4. Tumors can escape in many ways
5. Immunotherapy for tumors
Q: Why tumors still develop in the body if the immune system has the ability to recognize them?
How does cancer arise? II
Q: What causes dysregulated cell growth & proliferation?
• Intrinsic factors - Genetic mutations on Oncogenes & Tumor suppressor genes Environmental factors – Radiation, Carcinogens Microbial infections – Viruses (viral oncogenes) Bacteria
Key Concepts in Tumor immunity
1. Tumors express Ags that are recognized as foreign by the host immune system.
2. Immune responses frequently fail to prevent the growth of tumors.
3. The immune system can be activated by external stimuli to effectively kill tumor cells and eradicate tumors.
4. Various strategies have been developing to enhance the aBaidu Nhomakorabeati-tumor immune responses.
Tumors develop many ways to escape from immune attacks
Mechanisms of Tumor evasion
Treg infiltrating Tumors w/Fas
Tumor loss of MHC-I as a evasion mechanism
Lectures & Paper Discussion
• • Run the class with “Lectures” and “Paper discussion” Lectures deliver the basic concepts of fields.
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Paper discussion focuses on the latest articles related to specific topics.
Research Project discussion - Choose a type of cancer as the topic of cancer immunotherapy - Apply the knowledge from this course to cancer treatment
Paper & Project Discussion
1. 4 sections of Paper discussion and 2 sections of Project discussion
2. 2 paper presentations each time for 4 sections (Total 9 students)
3. 2 project presentations each time for 2 sections (Total 4 groups) 4. Each presentation: 40 min talk and 10 min discussion
Discovery of Immune surveillance of tumors
Discovery of Immune surveillance of tumors
1. Immune SurveillanceMacfarlane Burnet in 1950s 2. Use syngeneic mouse strain => Transplantation exp 3. Immunization w/ irradiated tumor X cells protects a syngeneic mouse w/ live X tumor cells but not Y tumor cells. 4. Antigens expressed by tumors, termed tumor antigens. 5. Defense against tumors is mainly mediated by T cells
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The Strategies for Cancer Therapy
The best scenario – Kill all the tumor cells without destroy others in the body 1. 2. 3. 4. 5. 6. Surgery – remove tumor cells & tissues physically Radiotherapy – non-selective, strong side effect Chemotherapy - non-selective, strong side effect Gene therapy – relatively selective Targeted therapy - relatively selective Immunotherapy => manipulate an immune response against tumor cells but not normal cells => quite selective
Immunoediting of Cancer
Dunn et al. Nature Reviews Immunology 6, 836–848 (November 2006) | doi:10.1038/nri1961
The progress in Immunology & Molecular Biology in past few decades make possible to manipulate the immune responses against tumors.
Introduction of Tumor Immunology
Goals of This Course
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Build up the concepts of Tumor Immunology
Learn the current development of Tumor Immunology, including immunotherapy & cancer vaccines. Not only deliver the knowledge but exercise thinking
4. Tumors can escape in many ways
5. Immunotherapy for tumors
Overview of Tumor Immunology
1. Tumorigenesis 2. Discovery of the protective immune response against tumors. 3. T cells recognize specific antigens on tumors
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Outline of Lecture Topics
• Discuss the interactions between the immune system and the cancer development, covering the following topics:
Basic concepts of tumor immunology
Tumor antigens arise by reactivated genes or overexpressed genes
Induction of T cell responses to tumors
Cross-priming (cross-presentation) mediated by APCs, ex. DCs
How does cancer arise?
Dysregulated cell growth & proliferation => Transformation
A clone of cells expanding indefinitely => A tumor
Tumor cells => the body and cause diseases => Cancer