Chapter 20 Tumor Immunology - PowerPoint PPT Presentation

Loading...

PPT – Chapter 20 Tumor Immunology PowerPoint presentation | free to download - id: 3d3ee1-ZDIzO



Loading


The Adobe Flash plugin is needed to view this content

Get the plugin now

View by Category
About This Presentation
Title:

Chapter 20 Tumor Immunology

Description:

Chapter 20 Tumor Immunology Introduction Part Tumor antigens Part Immune response to tumors Part Mechanism of tumor escape from immune ... – PowerPoint PPT presentation

Number of Views:714
Avg rating:3.0/5.0
Slides: 58
Provided by: jpkcSduE
Category:

less

Write a Comment
User Comments (0)
Transcript and Presenter's Notes

Title: Chapter 20 Tumor Immunology


1
Chapter 20 Tumor Immunology
2
Chapter 20 Tumor Immunology
Contents
  • Introduction
  • Part? Tumor antigens
  • Part? Immune response to tumors
  • Part ? Mechanism of tumor escape from
  • immune surveillance
  • Part? Immunotherapy of tumors

3
Introduction
  • Tumor immunology is mainly to study the
    immunogenicity of tumor and the mechanism of
    immune response to tumor, to demonstrate the
    relationship between the status of immune system
    and the generation, development of tumor, to
    explore the method of tumor diagnosis, therapy
    and prevention.
  • Immunosurveillance

4
Part? Tumor antigens
  • Tumor antigens Refer to all newly expressed
    antigens or over expressed antigens during the
    generation and development of the tumor.

5
?.Classification of tumor antigens
  • Base on their patterns of expression
  • Tumor specific antigen (TSA)
  • Tumor associated antigens (TAA)

6
1.Tumor-specific antigens (TSA)
  • TSA Antigens that are only expressed on tumor
    cells but not on normal cells. high specificity.
  • Tumor high-specific antigens
  • TSA---only expressed on one kind of tumor,
    induced by physiochemical factors, such as X-ray
  • Tumor low-specific antigens
  • TSA---expressed on more than one kind of
    tumor, induced by virus

7
Discovery of tumor specific transplantation
antigens, TSTA
?????????(methyl-cholanthrene,MCA)
8
Conclusion from this experiment
  • Tumors express antigens that are recognized as
    foreign by the immune system of the tumor-bearing
    host.
  • Immune response frequently fail to prevent the
    growth of tumors.
  • The immune system can be activated by external
    stimulator to effectively kill tumor cells and
    eradicate tumors.

9
2.Tumor-associated antigens,TAA
  • Antigens that are also expressed on normal cells,
    but high expressed on tumor cells. Without tumor
    specificity CEA, AFP

10
?.Common human tumor antigens
  • Embryonic antigens
  • Tumor antigens induced by viruses
  • proteins coded by Mutated oncogene or suppressor
    oncogene
  • TATAS expressed on human melanoma cells

11
1. embryonic antigens
  • embryonic antigens are proteins that are
    express at high levels on cancer cells and in
    normal developing fetal, but peter out or very
    low level in adult.
  • Their main function is that they provide markers
    that aid diagnosis of tumor.
  • Carcinoembryonic antigen (CEA)
  • alpha-fetoprotein (AFP)

12
(1) Carcinoembryonic antigen (CEA)
  • High CEA level is normally restricted to cells of
    the gut, pancreas, and liver in the course of 2-6
    months of gestation, and low level is found in
    serum of normal adult(lt5?g/ml).
  • CEA level of serum is increased in many
    carcinomas ,such as the colon, pancreas, stomach,
    and breast.
  • The level of serum CEA is used to monitor the
    persistence or recurrence of the tumors after
    treatment.

13
  • CEA levels in normal individuals are below 2.5
    ng/ml, but it increases significantly in certain
    malignancies, particularly colo-rectal cancers.
    It may also rise in some nonmalignant conditions
    (e.g., chronic cirrhosis, pulmonary emphysema,
    heavy smoking). Levels 4-5-fold of normal have
    been used to predict recurrence of colo-rectal
    tumors.

14
Carcinoembryonic antigen clinical use
  • Adjunct in diagnosis
  • Staging and prognosis
  • Monitoring response to therapy
  • Detection of tumor recurrence

15
Carcinoembryonic antigen clinical use
16
(2) alpha-fetoprotein (AFP)
  • AFP is a circulating glycoprotein normally
    synthesized and secreted by the yolk sac and
    liver of fetal.
  • Serum levels of AFP is very low in serum of adult
    (20ng/ml), and the concentration of AFP is up to
    500ng/ml in serum of patients with
    hepatocellular carcinoma.
  • higher rise in this protein is used for
    monitoring hepatomas and testicular cancers. AFP
    level may also be raised in some nonmalignant
    conditions, such as cirrhosis, hepatitis and
    other forms of liver damage.

17
Alpha fetoprotein concentrations
  • Normal concentration lt20 ng/ml
  • Abnormal concentrations
  • 100-350 possible hepatoma
  • 350-500 probable hepatoma
  • 500-100 likely hepatoma
  • gt1000 HEPATOMA

18
  • 2. Tumor antigens induced by viruses
  • HBV------ liver cancer
  • HPV------ cervical carcinoma
  • EBV------ B cell lymphoma and
  • nasopharyngeal carcinoma

19
  • 3. Products of mutated genes
  • Some tumor antigens are produced by mutated
    genes, such as suppressor oncogenes p53 and
    pro-oncogene ras

20
  • Some patients with cancer have circulating CD4
    and CD8T cells that can respond to the products
    of mutated genes such as Ras and P53.
  • Furthermore, in animals, immunization with
    mutated Ras or P53 proteins induces CTLs and
    rejection responses against tumors expressing
    these mutants.

21
  • Overexpressed cellular proteins and
  • abnormally expressed proteins
  • gp100, MAGE in melanomas
  • Cancer-testis antigens

22
Part? Mechanism Immune Response
  • T cells aßT,
    ?dT
  • NK cells
  • Cellular immunity
  • Macrophages
  • Dendritic
    cells
  • Humoral immunity

23
?.Cell-mediated Immune Response
  • T cells
  • NK cells
  • Macrophages(MF)
  • Dendritic cells (DCs)

24
  • 1. T lymphocytes
  • ??T cells
  • The principal mechanism of tumor immunity is
    killing of tumor cells by CTL
  • Tumor antigens
  • DC cross presentation

CD4Th cells
CD8T
(CTL)
25
(No Transcript)
26
(No Transcript)
27
  • (2) ??T cells
  • Non-class?MHC restriction
  • Its target cells are not hypersensitive to NK
    cells
  • First line of defence of immune surveillance

28
  • 2. NK cells
  • NK cells are broad-spectrum killer cells
  • It can kill target cells with low level or non
    MHC class ?molecule.
  • First line of defence of immune surveillance

29
NK????MHCI??????

KIR2DS KIR2DL
KIR2D KIR3D
DAP12 ITAM
????????????(KIR)(MHC-G)
ITIM
KIR2DL KIR2DS
CD94/NKG2AITIM CD94/NKG2C??DAP12 -ITAM
??????????(KLR) (HLA-E-9?)
30
activated
Tumor cell
31
  • 3. Macrophages(MF)
  • ? APC
  • ? release of lysosomal enzymes, reactive
  • oxygen intermediates, nitric oxide
  • ? ADCC
  • ? secrete cytokines
  • 4. Dendritic cells
  • ? APC------Induce adaptive immune response
  • ? Inhibit tumor growth directly

32
Antibodies ? Activating complement ? ADCC ?
Opsonization
?. Humoral immune responses
33
Antitumor Effector Mechanisms
CTL
NK cell
Tumor cell
Humoral Mechanisms
Macrophage
Kumar et al. Basic Pathology 6th ed. Figure 6-32
34
Part? Mechanism of Tumor Immune Escape
  • Factors related to tumor cells
  • Factors related to the hosts
  • immune system

35
?. Factors related to tumor cells
  • 1.low immunogenicity of tumor antigens and
    antigenic modulation
  • (1) low immunogenicity of tumor antigens
  • The failure of immunosurveillance may be the
    fact that in the early development of a tumor,
    the amount of antigen may be too small to
    stimulate the immune system.

36
Escape from immunosurveillance
Lack of Neo-antigens
37
  • (2) antigenic modulation is a phenomenon that
    cell-surface tumor antigens are decrease or lose
    because of attack of hosts humoral immune.

38
  • 2. covering or blocking of tumor antigens on the
    surface of the tumor cells

39
  • 3. Diminution or absence of MHC class I molecule
  • 4. Lack of co-stimulatory molecule on the surface
    of tumor cells
  • 5. Immune inhibitors secreted by tumor cells

40
(No Transcript)
41
Escape from immunosurveillance
42
?.Factors related to hosts immune system
  • 1. Immunodeficiency
  • 2. Suppressing immune function by tumor directly
    or indirectly

43
Parts ? immunotherapy of tumor
  • Active immunotherapy
  • Target immunotherapy
  • Adoptive immunotherapy
  • Cytokine therapy
  • genetherapy

44
Escape from immunosurveillance
Tumors shed their neo-antigens
45
  • Factors related to host
  • Poor immune function
  • Tumor inhibit immune function of host

46
Escape from immunosurveillance
Tumors secrete Immunosuppressive molecules
47
Part? Immunotherapy of tumors
  • Active immunotherapy
  • Target immunotherapy
  • Adoptive immunotherapy
  • Cytokine therapy
  • Gene therapy

48
  • Stimulation of active host immune
  • responses to tumors
  • Vaccination with tumor cells and tumor antigens,
    or with APC.
  • Augmentation of host immunity to tumors with
    cytokines and costimulators
  • Nonspecific stimulation of the immune system

49
  • Vaccination with tumor cells and tumor antigens

50
(No Transcript)
51
  • DC
  • Use primed dendritic cells
  • APCs can be fed tumor antigens in the laboratory
    and then injected into a patient. The injected
    cells are primed to activate T cells
  • Alternatively, DCs can be infected with a viral
    vector that contains the gene for a tumor
    antigen.

52
Use of tumor specific/associated antigens
monoclonal antibodies
53
  • Adoptive immunotherapy
  • Adoptive cellular immunotherapy is the
    transfer of cultured immune cells that have
    anti-tumor reactivity into a tumor-bearing host.
  • LAK, TIL, CD3AK, CTL

54
(No Transcript)
55
  • Passive immunotherapy for tumors with
  • T cells and antibodies
  • Therapy with anti-tumor antibodies
  • Monoclonal antibodies conjugated drugs
  • Adoptive cellular therapy
  • LAK,TIL,CD3AK,CTL

56
  • Cytokines may also be administered systemically
    for the treatment of human tumors.
  • IL-2 works by stimulating the proliferation and
    anti-tumor activity of NK cells and CTLs.
  • IFN-?works by increasing the cytolytic activity
    of NK cells and class I MHC expression on various
    cell types.
  • Their side effects limited this treatment.

57
  • Augmentation of host immunity to tumors with
    cytokines and costimulators
About PowerShow.com