Tumor Immunology - PowerPoint PPT Presentation

1 / 32
About This Presentation
Title:

Tumor Immunology

Description:

Carcinoma: Cancer of endo or ectoderm e.g. Skin or epithelial lining of organs ... eradicate tumor. Tumor Immunity. Innate Immunity. Macrophage. Natural killer cells ... – PowerPoint PPT presentation

Number of Views:872
Avg rating:3.0/5.0
Slides: 33
Provided by: CHAT56
Category:

less

Transcript and Presenter's Notes

Title: Tumor Immunology


1
Tumor Immunology
The ultimate goal of Tumor Immunology Induction
of clinically effective anti-tumor immune
responses in patients with pre-existing tumors
2
Types of Cancer
  • Carcinoma Cancer of endo or ectoderm e.g. Skin
    or epithelial lining of organs
  • Sarcomas Cancer of mesoderm e.g. bone, muscles
  • Leukemias and Lymphomas Cancers of hematopoietic
    cells

3
Evidence for Immunologic Defenses Against Cancer
in Humans
  • Immune cells around tumor mass
  • Hyperplasia of local lymph node
  • Increment of MHC class II and ICAM-1
  • Immunodeficiency is associated with increased
    incidence of cancers - B-cell lymphomas
  • AIDS
  • Transplant patients

4
The 10 leading Causes of Death in the US
5
Tumor Immunology
Characterization of tumor antigens Immune
responses to tumors Evasion of tumor from
immunosurvillance Immunotherapy
6
Immunologic Defenses Against Cancer in
Experimental Animals
  • Tumors induced by the same virus express the same
    virally determined antigens
  • Tumors induced by the same chemical are
    antigenically distinct
  • If a tumor is removed from a mouse, and the mouse
    later re-injected with the same tumor cells, no
    tumor will form

7
(No Transcript)
8
What are the Antigens Expressed on Tumors?
  • Tumor Specific Antigens (TSA)
  • Are only found on tumor cells.
  • Arise due to point mutations or rearrangement of
    cellular genes.
  • Can be derived from viral antigens of
    transforming viruses.
  • Tumor Associated Antigens (TAA)
  • Found on both normal and neoplastic tissue, but
    the expression is greatly altered/increased on
    cancer cells.
  • Oncofetal antigens are developmental antigens
    which become derepressed. (CEA and AFP)
  • Differentiation antigens are tissue specific.
  • Altered modification of a protein could be an
    antigen.

9
Tumor Immunity
-Tumors express antigens that are recognized as
foreign by the immune system of the
tumor-bearing host -Immune responses frequently
fail to prevent the growth of tumors -The immune
system can be stimulated to effectively kill
tumor cells and eradicate tumor
10
Tumor Immunity
Innate Immunity Macrophage Natural killer
cells Adaptive Immunity CTLs Antibody
11
Innate immune system I
  • Macrophages
  • are activated by IFN?
  • kill target cells by releasing TNF?, radical
    oxygen species, NO, and proteases

12
II
  • Natural Killer Cells (NK cells)
  • can mediate cytotoxicity of cells which have
    down-regulated their MHC I
  • part of the innate immune system involved in
    immune surveillance
  • mediate cytotoxicity by using perforin and
    granzymes, Fas L, and IFN?
  • NK deficient animals have a higher incidence of
    neoplastic disease

13
Innate Immunity NK cells
14
Adaptive Immunity
Cell-mediated immunity CD8 CTLs Humoral
immunity Antibody activating complement ADCC
(macrophage, NK cell)
15
Tumor Immunity
16
(No Transcript)
17
The Humoral Immune SystemWhat role does it play?
  • Antibodies may bind antigens on the tumor. This
    may result in
  • complement fixation on the tumor cell
  • antibody dependent cytotoxicity by NK cells,
    macrophages and CD8 killer T cells

18
Antibody Effector Functions
Carter P., Nature Rev Cancer.20011118-130
19
Mechanisms of Immunologic Cytotoxicity
  • Macrophage-mediated cytotoxicity
  • Natural killer cell-mediated cytotoxicity
  • T cell-mediated cytotoxicity
  • Antibody-dependent cell-mediated cytotoxicity
  • Complement-mediated cytotoxicity

20
(No Transcript)
21
How Does the Tumor Evade the Immune System?
  • Low immunogenicity low expression of adhesion
    molecules, MHC, co-stimulatory molecules, tumor
    antigens
  • Antigen the tumor may not express antigen
    against which the immune system is reactive.
    mutation of tumor antigens and antigen masking
  • Immunosuppression tumor cells may make compounds
    that suppress immune cells (MHC class 1). TGF-b
  • Speed of tumor growth may outpace the immune
    system
  • Antigen released may saturate the TCRs of T
    cells or released immunoglobulins

22
Cancer Immunotherapy

Active Immunotherapy Adjuvants Cancer
vaccines Cytokines Passive Immunotherapy Monoclo
nal antibodies In vitro-activated LAK
23
Adjuvants
Inflammatory substances BCG (macrophage
activator) Polyclonal activators of
T-lymphocytes anti-CD3 antibody (low dose)
24
Cancer Vaccines
Abbas,Lichtman and Pobber, Cellular and
Molecular Immunology. W.B. Saunders. 1999. Fig.
17-5
25
Cytokines
  • IL-2 ? increment of LAK and NK activity TNF, IL-1
    and IFN-gamma
  • TNF toxic in high level
  • IFN-alpha increment of NK activity and
    augmentation of MHC class I expression
  • IFN-gamma increment of NK and macrophage
    activities and augmentation of MHC expression

26
MHC Adenovirus- Induced Tumors
27
Cancer Immunotherapy

Active Immunotherapy Adjuvants Cancer
vaccines Cytokines Passive Immunotherapy Monoclo
nal antibodies In vitro-activated LAK
28
(No Transcript)
29
Monoclonal Antibodies
30
Cancer Immunotherapy

Active Immunotherapy Adjuvants Cancer
vaccines Cytokines Passive Immunotherapy Monoclo
nal antibodies In vitro-activated LAK
31
(No Transcript)
32
Treatment of Melanoma with LAK cells IL-2
Before
After
Write a Comment
User Comments (0)
About PowerShow.com