Download Immunology and Cancer

Immunology and Cancer
and
Some Concepts on
Non-Immunological
Host-Response in Cancer
Folder Title: CxImmuno(NoTP)
Updated: April 13, 2013
TtlCxImm
Vaccination of Mice
with Irradiated Killed
Tumor Cells
Figure 15.17 The Biology of Cancer (© Garland Science 2007)
p. 673
Immune Response in Cancer
1.
2.
3.
4.
5.
6.
7.
When it works, what does it “See”?
What target or targets does it attack?
What “weapons” does it attack with?
Why do some tumors regress?
Why doesn’t the immune response work better in cancers?
Can the immune response in cancer make the pathology worse?
How can we make the immune response works better in cancer?
Specific Adaptive Immune
Responses:
Humoral:AntibodyAntigen
(Uses Antibodies to
recognize Targets)
Cell-Mediated:
Helper and Cytotoxic TCells
(Uses T-Cell Receptors to
Recognize Targets)
Anti-Cancer Effector Mechanisms
Humoral:
Antibody and complement
Lymphokines and other cytokines
Cell-Mediated Immunity:
Cytotoxic T-Cells
Natural Killer Cells (NK Cells)
Activated Killer Cells
Activated macrophages
Lymphokine-activated Lymphocytes
Granulocytes
Combined Humoral and Cell-mediated:
Antibody-dependent Cell-mediated Cytotoxicity
Figure 15.3b The Biology of Cancer (© Garland Science 2007
p. 658)
Figure 15.12d The Biology of Cancer (© Garland Science 2007) p. 666
Potential Tumor Antigen Targets
From Pitot
CxAgsPitot
Login as registered user
Ludwig Institute For Cancer Research
Academy of Cancer Immunology
European Cancer Immunome Program
Please, register before using the database.
Registration as a Cancer Immunome Database user is free and open, but necessary for anyone wanting access to the data. If you wish to contribute
data to the CID, the username and password that you select guarantee that the information you deposit will be properly attributed, and that you alone
(or
members
of
your
lab,
if
the
lab
is
already
registered)
will
have
the
right
to
modify
it.
Please, contact CID manager should you have questions or problems.
Have forgotten your password?
http://ludwig-sun5.unil.ch/CancerImmunomeDB/
Cancer Antigen Database: “Immunome” ; Ludwig Institute for Cancer Research
Should the Biology of Cancer course be retained as an
undergraduate major course in Biology?
This question is set to anonymous. I will not know what choice you selected and this is not graded. Biology of Cancer is not a usual
course for a Biology Department. We have had this course going for 35 years. Should we keep it or drop it? (multiple choice)
Responses
Drop it. It belongs in a medical school.
1
1.28%
22
28.21%
55
70.51%
0
0%
78
100%
Keep it, but it needs a lot of improvement to be as valuable as it could be in an undergraduate biology program.
Keep it. It is a valuable option among our undergraduate courses.
No opinion on this.
Totals
80.00%
0%
70.5%
70.00%
60.00%
50.00%
28,2%
40.00%
28.2%
30.00%
20.00%
10.00%
1.3%
0%
0.00%
Drop it. It belongs in a Keep it, but it needs a
medical school.
lot of improvement to
be as valuable as it
could be in an
undergraduate biology
program.
Series1
Series2
Keep it. It is a
valuable option
among our
undergraduate
courses.
Series3
Series4
No opinion on this.
General Concepts on Host-Response
in Cancer (Part 1)
Does the Host Respond to Prevent
Oncogenesis?
Does the Host Respond to Limit Neoplastic
Growth and Progression?
If So, How Does the Host Respond?
What Exactly Is the Host Recognizing?
• To Prevent Oncogenesis
• To Limit Growth and ProgressionGenResp1
General Concepts on Host-Response
in Cancer (Part 2)
Is the Appearance and Growth of Cancer Related to
Weakened Host Response?
Genetically Weakened?
Environmentally Weakened?
Physiologically or Pathologically Weakened?
Can Host Response Actually Facilitate Tumor
Appearance and Enhance Tumor Growth
and Progression?
Can the Recognition and Response Mechanisms be
Mobilized, Enhanced, and Directed for
Cancer Management and Cancer Therapy?
Can They Be Used in Cancer Prevention?
GenResp2
Cells and Factors in the Natural Immune
Response in Cancer
Natural Killer (NK) Lymphocytes
• Non-B-Cell, Non-T-Cell "Null" Lymphocytes
• Activated by Interferon
Activated Macrophages
• Includes Splenic MPh's, Liver Kupfer Cells, Alveolar
(Lung) MPh's, Brain Glial Cells, and others
Granulocytes (Polymorphonuclear Leucocytes)
• Neutrophils, Eosinophils, Basophils, Tissue Mast Cells
Activated Non-Antigen-Specific T-Cells
• Lymphokine-activated Killer Cells (LAK)
Cytokines
• Tumor Necrosis Factor (TNF), Interferons
• Interleukins (e.g. IL-2)
CxNatImm
Tumor Escape Mechanisms and
Immune-mediated Tumor Enhancement
1.
Serum blocking factors
2.
Surface Antigen Shedding
3.
Antigenic Modulation (Internalization of antigens)
4.
Defective complement components
5.
Host genetic limitations
6.
Absence of tumor specific rejection antigenic targets
7.
Localized concentration of effector mechanisms and distant tumor sites and
host unresponsiveness.
8.
Immunologically privileged sites.
9.
Immune suppression by viruses, tumor products, illness, or medical
intervention (e.g. surgery or radiation)
10. Generation of suppressor cells and suppressor factors
11. Sneaking through by early low levels of tumor targets followed by
enhancement or unresponsiveness (tolerance)
Non-Specific Innate Natural Immunity vs Specific
Adaptive Immunity in Cancer
Innate Natural Immunity
Specific Adaptive Immunity
No Specific Antigen Recognition
Specific Antigen Recognition
Not Antibody-dependent
Can Involve Antibodies
No Antigen-specific T-Cell Receptor Uses T-Cell Receptors
Not MHC-Restricted
MHC-Restricted
(Recognizes Altered-self)
No Memory Response
Exhibits Immunological
Memory
No Priming & Second-set Response Enhanced Secondary
Responses
No Clonal Selection & Expansion
Involves Clonal Selection and
Expansion of T- and B-Cells
Non&Spec
Co-stimulatory and co-receptor molecules
in the specific adaptive immune response:
Immune escape mechanisms in cancer
MHC
Class I
Modulation
and
Escape from
T-Cell
Lysis
from Kuby,
Immunology
MHCEscap
TnBTargets
From Pitot
Non-Immunological Host-Responses
in Cancer
Anti-carcinogenic Effects: Deactivation, Elimination
DNA Repair Mechanisms
Genetically-directed Apoptosis
(May Function in Anti-tumor Immunity Also)
Differentiation-inducing Factors
Oncolytic Cytokines
(May Function in Anti-tumor Immunity Also)
Hormonal Responses
Anti-Angiogenesis Factors Affecting Tumors
Psychological Factors
(May Function in Anti-tumor Immunity Also)
NonImmRe