The Immune System & Cancer Flashcards
The Immune System & Cancer
Cancer cells
what triggers a mutation?
Mutations triggered by chemicals,
radiation, viruses, or inherited defects
in regulatory genes
The Immune System & Cancer
Cancer cells
After a mutation is triggered what happens?
Cells proliferating in an uncontrolled
fashion will give rise to a growing
clone of cells that eventually develops
into a tumor or neoplasm
The Immune System & Cancer
Cancer cells
what mechanisms are involved in tumor supression?
Several mechanisms are involved in
tumor suppression: DNA repair,
cellular senescence, etc
Apoptosis
The Immune System & Cancer
Cancer cells
Tumor Antigens
Name 3
- Neoantigens
- Oncogenic Viruses Antigens
- Overexpressed Cellular Proteins
see slides for diagrams
The Immune System & Cancer
Cancer cells
Tumor Antigens
what is a neoantigen?
- Neoantigens
– Encoded by mutated genes
– Not found on normal cells
– A single tumor can express several neoantigens
The Immune System & Cancer
Cancer cells
Tumor Antigens
what is a Oncogenic Viruses Antigens
Oncogenic Viruses Antigens
– May elicit responses against the tumors
– Epstein-Barr virus, Papillomavirus
The Immune System & Cancer
Cancer cells
Tumor Antigens
what is a * Overexpressed Cellular Proteins
Overexpressed Cellular Proteins
– Expression for longer times or at different locations
– Abnormally high levels of expression
The Immune System & Cancer
Cancer cells
Tumor Antigen
The Immune System & Cancer
Cancer cells
Immune surveillance
3 theories: 1909 Paul Erlich
1909 - Paul Erlich
– Hypothesis that host defense may
prevent neoplastic cells from developing
into tumors
The Immune System & Cancer
Cancer cells
Immune surveillance
3 theories: 1953 Gross and Foley
- 1953 - Gross & Foley
– Evidence of tumor stimulated IR
The Immune System & Cancer
Cancer cells
Immune surveillance
3 theories: late 1950’s MacFarlene Burnet
- Late 1950s - MacFarlene Burnet
– Tumor cell neoantigens induce an IR
against cancer
– Immune surveillance theory
**see slide for diagram
The Immune System & Cancer
Cancer cells
Cancer Immunoediting
- 2002 - Dunn and Schreiber explain
Cancer Immunoediting
- 2002 - Dunn and Schreiber
– Elimination phase
* Tumor cells are killed by NK, CD4+ and CD8+ cells
– Equilibrium phase
* When the immune system is unable to destroy the tumor
– Escape phase
* Appearance of clinically detectable tumors
The Immune System & Cancer
Cancer cells
Immune Surveillance - Elimination
* Innate immune mechanisms
what are they, how does it work?
Immune Surveillance - Elimination
- Innate immune mechanisms
– Neutrophils
* Produce TRAIL (TNF-related apoptosis-inducing ligand)
* Stimulates apoptosis in tumor cells
– NK cells
* Express NKG2D which can bind MICA and MICB on
many tumor cells
**see slide for below diagram
NK cells
- Failure to express MHC I
- Expression of
nonclassical molecules
(MICA or MICB)
The Immune System & Cancer
Cancer cells
Immune Surveillance - Elimination
Macrophages
How does this work?
Macrophages
– Classically activated M1 macrophages can kill many tumor cells
– Possibly recognized by DAMPs from dying tumor cells through
macrophage TLRs
– Activation of macrophages by IFN-γ produced by tumor-specific T
cells
– Production of nitric oxide (NO)
– M2 macrophages have been known to promote tumor growth
through secretion of vascular endothelial growth factor (VEGF)
and TGF-β
The Immune System & Cancer
Cancer cells
Immune Surveillance - Elimination
- Adaptive immunity mechanisms
3 ways, how do they work?
- Adaptive immunity mechanisms
– CD8+ T cells - Specific for tumor peptides presented on MHC class I can directly
lyse tumor cells using perforins and granzymes
– CD4+ T cells
* Activated by APCs presenting tumor antigens leading to direct or
indirect destruction of the tumor
* IFNγ produced by CD4+ T cells activates macrophages
– NKT cells
* Recognize antigen presented by non-classical MHC class I
molecules on tumor cells
The Immune System & Cancer
Cancer cells
Immune Surveillance - Elimination
- Adaptive immunity mechanisms
How do these work (2 ways)
– Tumor-bearing hosts may produce antibodies against
various tumor antigens
– Antibodies may kill tumor cells by activating complement
or by antibody-dependent cell-mediated cytotoxicity
The Immune System & Cancer
Cancer cells
what is equilibrium?
- State in which tumor cells
remain but do not progress - Tumor cells are not completely
eliminated, but neither do they
proliferate
The Immune System & Cancer
Cancer cells
Tumor Escape
4 steps what are they? Explain?
- TGF-β
- Induces tumor cell proliferation and
angiogenesis - Suppresses elements of the host
antitumor immune response - Indoleamine2,3-dioxygenase (IDO)
- Suppresses T-cell proliferation
- Galectin-1
- Stimulates angiogenesis
- Programmed cell death ligand 1 (PDL1)
- Slow down immune responses
The Immune System & Cancer
Cancer cells
Tumor Escape
what is: * TGF-β
- TGF-β
- Induces tumor cell proliferation and
angiogenesis - Suppresses elements of the host
antitumor immune response
The Immune System & Cancer
Cancer cells
Tumor Escape
what is: * Indoleamine2,3-dioxygenase (IDO)
- Indoleamine2,3-dioxygenase (IDO)
- Suppresses T-cell proliferation
The Immune System & Cancer
Cancer cells
Tumor Escape
what is: * * Galectin-1
- Galectin-1
- Stimulates angiogenesis
The Immune System & Cancer
Cancer cells
Tumor Escape
what is: ** Programmed cell death ligand 1 (PDL1)
- Programmed cell death ligand 1 (PDL1)
- Slow down immune responses
The Immune System & Cancer
Cancer cells
Tumor-associated Macrophages
M2 Macrophages explain
Tumor-associated Macrophages
17
M2 Macrophages
Can generate an
anti-inflammatory environment
within the tumor
**see diagram
The Immune System & Cancer
Cancer cells
Immunological Escape Mechanisms
explain what the 4 features and how they work
Immunological Escape Mechanisms
- Highly similar to self
– No PAMPs - Not all cells will express the same neoepitopes
- Switch off T-cell responses
– IL-10 or TGFβ - T-cell checkpoint molecules
– CTLA-4, PD-L1
– Anergy
