introduction of tumor immunology pin ling ( 凌 斌 ), ph.d. ext 5632; [email protected]...
TRANSCRIPT
Introduction of Tumor Immunology
Pin Ling ( 凌 斌 ), Ph.D. ext 5632; [email protected]
• References: 1. Tumor Immunology and Cancer Vaccines (Samir Khleif, Publisher: Springer; 1st edition 2005)
2. Cancer Immunotherapy-Advances in Immunology, Vol. 90 (James Allison, Glen Dranoff; Publisher: Academic Press 2006)
3. “Cancer Immunology and Immunotherapy” in Current Topics in Microbiology and Immunology, Vol 344, 2011
Goals
1. Build up the Concepts of “Tumor Immunology”.
2. Discuss the “Current Progress” of Tumor Immunology, including Tumor-immune system interaction, Immunotherapy, & Cancer Vaccines.
3. Run the course with “Lectures”, “Paper Discussion”, & “Research Proposal”
Outline of Lecture Topics
Discuss the interactions between the immune system and the cancer development, covering the following topics:
(1) Basic Tumorigenesis
(2) Inflammation & Cancer
(3) Immunosurveillance and Immunoediting of Cancer
(4) Mechanisms of Immune Evasion by Tumors
(5) Cancer Vaccine Development & Cancer
Immunotherapy
Lectures, Paper Discussion & Research
Proposal1. “Lectures” deliver the basic concepts of fields.
2. “Paper discussion” focuses on the latest articles related to specific fields.
3. Research Project Discussion- Choose a type of cancer as the topic of
cancer immunotherapy or other tumor immunology
topics - Apply the knowledge from the basic science to the cancer treatment
4. Not only deliver the “Knowledge” but exercise “Problem-solving” & “Thinking”
1. 4 sessions of Paper discussion and 2-3 sessions of Project discussion
2. 2 presentations for each paper discussion (depends on total students)
3. Each paper presentation: 30-40 min talk and 10 min discussion
Paper & Project Discussion
Team work is the key! Everyone should get involved in paper and project discussion
1. Propose a research project to study topics
in Tumor Immunology or Cancer immunotherapy
2. Abstract presentation: 20 min/each team and 5-10 min discussion - Prepare one-page written abstract & 20
min talk to present your team’s idea - Short Rationale (Background), Main
goal, approaches (specific aims), & potential problems.
Research Project Discussion
3. Full proposal presentation: 30-40 min talk
and 10 min discussion - Like Abstract, extend each parts,
Rationale, Specific aims, & Alternatives (for potential problems)
- Turn in a written full proposal (around 10
pages)
Research Project Discussion
1. Exercise “Scientific Approaches” - How to translate your scientific knowledge into
scientific advancement & clinical applications
2. Emphasize on Originality, Logic Thinking & Extensiveness (1) Identify a key problem or challenge in the field (2) Form a hypothesis (Originality & Novelty) (3) Layout the approaches (specific aims) (Logic Thinking) (4) Alternatives (potential problems)
(Comprehensiveness)
3. Avoid to repeat an approach from Cancer A to Cancer B
Keys to a research proposal
If you are still unclear, Check with your advisor or me after class Check post-docs or senior PhD students in your lab
Reading (Papers)
Writing (Proposal)
Listening (Lectures)
Speaking (Presentation)
Inputs Outputs
Key Elements in Learning
EvaluationEvaluation
1. 上課出席率 (Attendance) 50%
2. 專題報告 (Paper, Research Project Discussion, and Written Proposal) 30%
3. 課堂表現 (Class Performance) 20%
1. Tumorigenesis
2. Overview of the immune system3. T cells recognize specific antigens
on tumors
4. Tumors can escape in many ways
5. Manipulate the immunity against
tumors
6. Cancer Immunotherapy
Overview of Tumor Immunology
How does cancer arise?
Dysregulated cell growth & proliferation => Transformation
A clone of cells expanding indefinitely => A tumor (continuously evolved)
Tumor cells => the body and cause diseases (Metastasis) => Cancer
How does cancer arise? How does cancer arise? IIII
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
The Strategies for Cancer Therapy
The best scenario –Kill all the tumor cells without destroying normal cells in the body
1. Surgery – remove tumor cells & tissues physically
2. Radiotherapy – non-selective, strong side effect
3. Chemotherapy - non-selective, strong side effect
4. Gene therapy – relatively selective5. Targeted therapy - relatively selective =>
successful cases growing6. Immunotherapy => manipulate an immune
response against tumor cells but not normal cells
1. Tumorigenesis
2. Overview of the immune system3. T cells recognize specific antigens
on tumors
4. Tumors can escape in many ways
5. Manipulate the immunity against
tumors
6. Cancer Immunotherapy
Overview of Tumor Immunology
Key concepts about immunity-I
1. The immune system has evolved to (1) Protect against the invading pathogens (or foreign substances) and to (2) Maintain tissue homeostasis (damaged cells or cancer). Meanwhile, microbes (outside) and tumors (inside) have
evolved to survive in the host.
2. The immune system (in vertebrates) consists of (1) Innate immunity and (2) Adaptive immunity => An integrated system of host defense => Cells & molecules function cooperatively Antigen-presenting cells => Lymphocytes => Effector cells
3. Innate immunity is evolutionally the more conserved host defense system:
- Existed in both Invertebrates & Vertebrates - Provides the first line of defenses against infections - “Activates” and “Programs” adaptive immune responses
Key concepts about immunity-II
5. Adaptive immunity evolved later: - Existed only in Vertebrates - Provides the more potent and diverse defenses
against infections - Develops as a response to infection and adapts to the
infection
6. The immune system may fail => Immunodeficiency, Hypersensitivity, & Autoimmune diseases.
7. Normal immune responses can be obstacles in medical cases, e.g., organ transplantation
Better Understanding of Immunology Help manipulate immune responses Solve the medical problems
PRRs for sensing infectious & PRRs for sensing infectious & endogenous signalsendogenous signals
1. PRRs (Pattern Recognition Receptor)
for:(1) PAMPs from pathogens(2) DAMPs (DangerAssociated Molecular Patterns) from host cells
2. Deregulated immuneresponses to these
stimulileading to• Infectious diseases• Autoimmune
disorders• Allergy • “Cancer
development”
Interactions between innate and
& adaptive immunity1. Innate immunity => Ag presentation (by Dendritic cells)
2. Adaptive immunity => Ag recognition (by T & B lymphocytes)
Immune Recognition of Tumors
1. Syngenic mouse strain
=> the immune response
against tumors
2. Immunization w/ irradiated tumor X cells protects a syngenic mouse w/ live tumor X cells but not tumor Y cells.
3. Antigens expressed by
tumors, termed Tumor Antigens.
Q: How do tumor antigens (Ags) arise?
Tumor Ags arise from many ways:(1) Mutations or translocations on self genes(2) Abnormal expression of self gene products (3) Reactivation of germ cell genes(4) Viral oncogenes
Natural Killer (NK) Cells
1. Another weapon for anti-
Tumor immunity
2. Kill tumor cells losing MHC-I
Q: Why tumors still develop in the body if the immune system has the ability to recognize them?
Most clinical cancer cases represent the situation that Tumors outsmart the host immune system
Tumors develop many ways to escape from immune attacks
Tumors use immune cells to help their development
Paradoxical roles of the immune system in cancer
development1. Mechanisms against cancer development: (1) Cellular immunity- T, NK, & Other innate
immune cells (2) Humoral immunity- Cytokines, Abs, ..etc
2. Mechanisms promoting cancer development:
(1) Inflammation => angiogenesis & tissue remodeling
(2) Enhance survival pathways (NF-kB) (3) Suppression of anti-tumor immune responses
The progress in Immunology & Molecular Biology in past decades make possible to manipulate the immune responses against tumors.
Enhance Tumor Immunogenicity
Enhance CTLs & NK Killing ability
Change Tumor Microenvironment
Discovery of Immune recognition of
tumors
1. Use syngenic mouse strain=> the immune response
against tumors
2. Immunization w/ irradiated tumor X cells protects a syngenic mouse w/ live tumor X cells but not tumor Y cells.
3. Antigens expressed by tumors, termed Tumor
Antigens.
The Interface between innate and adaptive
immunity1. Innate immunity => Ag presentation (by dendritic cells)
2. Adaptive immunity => Ag recognition (by T & B lymphocytes)