Introduction of Tumor Immunology

Bei-Chang Yang ( ), Ph.D.

Department of Microbiology & Immunology
ext 5637; y1357@mail.ncku.edu.tw
Pin Ling ( ), Ph.D.
ext 5632; lingpin@mail.ncku.edu.tw
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)

Goals of This Course

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

Outline of Lecture Topics

Discuss the interactions between the immune

system and the cancer development, covering the
following topics:

(1)

Basic concepts of tumor immunology

(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

Lectures & Paper Discussion

Run the class with Lectures and Paper discussion

Lectures deliver the basic concepts of fields.

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

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

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

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

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

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 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

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

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

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

class-I but express ligands for activating NK cells.
b. Macrophages => Ab-med phagocytosis
=> Cytokines (TNF-a), ROS, & NO

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

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

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 evasion

Treg infiltrating
Tumors w/Fas

Tumor loss of MHC-I as a evasion

mechanism

Immunoediting
of Cancer

Dunn et al. Nature Reviews

Immunology 6, 836848 (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.

Enhancing Tumor Immunogenicity

Enhancing Anti-Tumor Responses

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

Tumor vaccines-Targeting DCs

Types of Tumor Vaccines

Enhancement of tumor
immunogenicity

Immunotherapy with cytokine

gene-transfected tumor cells

Systemic cytokine therapy for tumors

Passive
Immunotherapy
for tumors
Adoptive cellular therapy

Therapy with Anti-tumor

Monoclonal Abs

Approved Anti-tumor mAb

SUMMARY
1. 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 18

SCIENCE VOL 319 11 JANUARY 2008

Recognition of a Ubiquitous Self Antigen by Prostate

CancerInfiltrating 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.
OBrien CA, Pollett A, Gallinger S, Dick JE.
Division of Cell and Molecular Biology, University Health Network, Toronto, Ontario,
M5G 1L7, Canada.

The End & Thank you