Introduction of Tumor Immunology. Bei-Chang Yang ( 楊倍昌 ) , Ph.D. Department of Microbiology & Immunology ext 5637; [email protected] Pin Ling ( 凌 斌 ), Ph.D. ext 5632; [email protected] References: 1. Tumor Immunology and Cancer Vaccines - PowerPoint PPT Presentation
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Introduction of Tumor Immunology
• Bei-Chang Yang ( 楊倍昌 ), Ph.D.Department of Microbiology & Immunologyext 5637; [email protected]
The Strategies for Cancer The Strategies for Cancer TherapyTherapy
The best scenario – Kill all the tumor cells without destroy others in the body
1. Surgery – remove tumor cells & tissues physically 2. Radiotherapy – non-selective, strong side effect3. Chemotherapy - non-selective, strong side effect4. Gene therapy – relatively selective5. Targeted therapy - relatively selective6. Immunotherapy => manipulate an immune
response against tumor cells but not normal cells => quite selective
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
anti-tumor immune responses.
Discovery of Immune surveillance
of tumors
Discovery of Immune surveillance
of tumors1. Immune Surveillance- Macfarlane 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
Immune surveillance of tumors-II
Identification of tumor Ags by CTLs
Examples of tumor antigens-I
Examples of tumor antigens-II
Tumor antigens arise by point mutations in self
proteins
Tumor antigens arise by reactivated genes or overexpressed genes
IInduction nduction of of T cell responses to T cell responses to tumortumorss
Cross-priming (cross-presentation) mediated by APCs, ex. DCs
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
2. Innate immune responses to tumors: a. NK cells kill many types of tumor cells that have reduced clas
s-I but express ligands for activating NK cells. b. Macrophages => Ab-med phagocytosis => Cytokines (TNF-a), ROS, & NO
1. Tumorigenesis
2. Discovery of the protective immune response against tumors.
3. T cells recognize specific antigens on tumors
4.4. Tumors can escape in many waysTumors can escape in many ways
5. Immunotherapy for tumors
Overview of Tumor Immunology
1. Tumorigenesis2. Discovery of the protective immune response aga
inst tumors.3. T cells recognize specific antigens on tumors
4. Tumors can escape in many ways5. Immunotherapy for tumors
Overview of Tumor Immunology
Q: Why tumors still develop in the body if the immune system has the ability to recognize them?
Tumors develop many ways to escape from immune attacks
Mechanisms of Tumor Mechanisms of Tumor evasionevasion
Tumors w/Fas
Treg infiltrating
Tumor loss of MHC-I as a evasion mechanism
Dunn et al. Nature Reviews Immunology 6, 836–848 (November
2006) | doi:10.1038/nri1961
Immunoediting of Cancer
The progress in Immunology & Molecular Biology in past few decades make possible to manipulate the immune responses against tumors.
Enhancing Tumor Immunogenicity
Enhancing Anti-Tumor Responses
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. 5. Immunotherapy for tumorsImmunotherapy for tumors
Overview of Tumor Immunology
Tumor vaccines-Targeting DCs
Types of Tumor Vaccines
Enhancement of tumor immunogenicity
Immunotherapy with cytokine gene-transfected tumor cell
s
Systemic cytokine therapy for tumors
Passive Immunotherapy for tumors
Adoptive cellular therapy
Therapy with Anti-tumor Monoclonal Abs
Approved Anti-tumor mAb
SUMMARY1. Cancer is a complex and progressive genetic disease.
2. Tumors express Ags that could be recognized by the immune system. But some tumors are weakly immunogenic and the immune system often fails to eradicate them.
3. Cancer from clinical cases usually represents the leading of cancer development over the anti-cancer immune responses.
4. The imperative issue in the field of tumor immunology is
to improve the capability of immune defenses to fight cancer.
Paper Discussion on March 18SCIENCE VOL 319 11 JANUARY 2008
Recognition of a Ubiquitous Self Antigen by Prostate Cancer–Infiltrating CD8+ T Lymphocytes
Peter A. Savage,1 Keith Vosseller,2 Chulho Kang,3 Kevin Larimore,4 Elyn Riedel,5Kathleen Wojnoonski,1 Achim A. Jungbluth,6 James P. Allison1*
Nature. 2007 Jan 4;445(7123):106-10. Epub 2006 Nov 19
A human colon cancer cell capable of initiating tumour growth in immunodeficient mice.
O’Brien CA, Pollett A, Gallinger S, Dick JE.Division of Cell and Molecular Biology, University Health Network, Toronto, Ontario, M5G 1L7, Canada.