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33 Cards in this Set

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Why are cancers not considered a "single" disease?
There is extreme variability with respect to:
- Cell type
- Molecular alterations
- State of differentiation
What components of an animal immune to a tumor provides protection when injected into a naive animal which is then subjected to that same tumor?
Cell mediated immune response:
- T cells
- CD8 cells
- CD4 cells (depends on tumor)
What causes the immune system to recognize a tumor when the tumor originated from self-cells?
Tumor cells express immunogenic antigens
What are some mechanisms by which immunogenic antigens develop on tumor cells?
Oncogenic virus → viral protein

Mutagen → mutant protein

Chromosomal rearrangement → fusion protein

Mutation → de novo expression
What are two reasons why the immune system might recognize self-antigens?
Intolerance to self-antigen

Low affinity (weak) responses always present
How do T cells detect tumor antigens?
Dendritic cells present antigen via MHC I / II pathways and then go to lymph nodes for recognition by T cells
How do effector CD8 T cells seek out and destroy the tumor?
The tumor antigens are broken down via proteosomes and presented via MHC I

Primed CD8 T cells find these MHC I complexes with tumor antigen and destroy the tumor
Why are CD4 T cells less involved in the immune response against a tumor than CD8 T cells?
Many tumors are MHC II negative, thus do not get recognized by effector CD4 T cells
How do effector CD4 T cells seek out and help the destruction of tumor cells?
Two ways:
1. If the tumor expresses MHC II, CD4 T cells can directly seek these tumor cells and help destroy them

2. APCs around the tumor present tumor antigen on MHC II, which are recognized by CD4 T cells, leading to inflammation and tumor destruction
What are the mechanisms by which the immune system kills tumor cells?
CD8 T cells (cytotoxic T cells) recognize MHC I on tumor and kills cells

Tumor antigen attracts macrophages which:
- Attract CD4 T cells via MHC II
- Release cytokines and reactive oxygen species
What do CD4 T cells do once they are recruited to a tumor?
Secrete TNF which leads to inflammation
How can a tumor escape immunosurveillance?
Lose MHC I

Tolerance

Immunosuppression

Lack or loss of antigen
How are tumor cells that have lost MHC I proteins still killed by the immune system?
NK cells
How do NK cells avoid killing host cells?
NK cells recognize MHC I on host cells via NK inhibitory receptor and are turned off
How do NK cells kill tumor cells that have lost MHC I proteins?
NK cell inhibitory receptors on NK cells do not see MHC I on tumor and are turned on

(Also need a second "on" signal)
What are ways that a tumor can evade host responses?
The tumor is not sufficiently immunogenic, lacking recognizable antigen

The tumor impairs the host response
- Tolerance
- Tumor is immunosuppressive

Failed presentation of antigen
- Loss of MHC I
- Loss of tumor antigen expression

Tumor overwhelms immune system
Why is immunotherapy an attractive choice for cancer treatment over surgery, chemotherapy, or radiation?
High specificity

Precise locating of tumor cells

Memory
What are the four immunotherapeutic strategies against cancer?
Non-specific immune stimulation
- Jazzes up immune system

Antibody immunotherapy

Increase pre-existing immune responses
- Amplify original anti-tumor immune response

Stimulate new immune response (and/or existing response)
How is the method of non-specific immune stimulation accomplished?
Infect patients to boost immune response
What was the general mechanism of non-specific immune stimulation?
1. Infect patient with bacteria

2. Bacteria cause macrophages to secrete TNF

3. TNF leads to vessel thrombosis, cutting off blood supply to tumor
What was the problem with non-specific immune stimulation and what is the one case in which it seemed to benefit patients?
TNF is too toxic

Response against BCG (mycobacterium) infection has some localized effect in bladder cancer
What are the ways by which antibodies used in antibody immunotherapy can kill tumor cells?
Antibody-induced complement activation:
- Lysis
- NK cells and macrophage recruitment for antibody-dependent cellular cytotoxicity (ADCC)

Anti-proliferative antibodies

Pro-apoptotic antibodies

Toxin-conjugated antibody

Radioactive-antibody
What is an example of an anti-proliferative antibody used for immunotherapy?
Her2neu for breast cancer
What is an example of a pro-apoptotic antibody used for immunotherapy?
CD20 against lymphoma
What are ways by which pre-existing immune responses to the tumor are amplified?
IL-2 therapy

Adoptive cellular therapy

Inhibit inhibitory T cell actions
What is the general mechanism of IL-2 therapy?
Cause proliferation in T cells
What are cons of IL-2 therapy?
Toxicity

Limited efficacy
What is the general mechanism of adoptive cellular therapy?
1. Expand patient's anti-tumor T cells ex-vivo

2. Re-infuse patient with expanded T cells (or lymphocyte activated killer cells from monocytes activated by IL-2)
What is an example of inhibiting the inhibitory T cell responses?
Antibody blocking CTLA4 (inhibitory receptor on T cells and on inhibitory T cells)
What is a con of inhibiting the inhibitory receptors of T cells?
Can lead to autoimmunity
How are new immune responses stimulated?
Prophylactic vaccines

Cancer antigen-dendritic vaccine
What is an example of a prophylactic vaccine against cancer?
HPV vaccine
What is the mechanism of using a cancer antigen-dendritic cell vaccine?
1. Grow dendritic cells with specific antigen and cytokine

2. Re-infuse patient with cells