Unit 22 - Tumor Immunology Flashcards
What is the immune surveillance Theory?
Immune systems’ job is to check for tumors!
What is the evidence used to support the Immune Surveillance Theory?
- Immunosuppressed patients have increase in tumors.
- Tumor Infiltrating Lymphocytes = better prognosis
- Some tumors spontaneously regress due to immune response.
What is the evidence against the Immune Surveillance Theory?
Tumors do not increase in immunosuppressed patients randomly - there are specific ones that increase (oral, skin, lymphoid).
Nude mice have no T-cells and they do not get tumors. (they have very good, very reactive NK Cells)
Is the Immune Surveillance Theory promising?
Yes! It has a good argument for immune specificity to tumors.
Is the Immune Surveillance Theory promising?
Yes! It has a good argument for immune specificity to tumors.
What is immunoediting? EEE
Tumor cells have Ag!
Eliminate: immune system eliminates tumor cell
Equilibrium: tumor and lymphocytes exist in equilibrium (lymphocytes are in the tumor but don’t destroy it)
Escape: tumor cells fight back and avoid immunity
How do tumor cells “escape”?
- alter their Ag
- Shed their Ag
- Down regulate MHC-1 to avoid NK Cells
- Secrete TGF-beta cytokine to decrease immune response
What is the innate immunity’s importance for tumors?
The dendritic cells and macrophages are important! Inflammation is a valuable tool.
Ex: mycobacterium and bladder cancer = inflammation = tumor regresses
What are TAA’s?
Tumor Associated Antigens
Ag on tumors that is not normally found on the normal versions of the cell.
What are the TAA’s that are recognized by the immune system called?
TRA’s! Tumor Rejection Antigens
Super important to identify for future targeting and treatment
What viruses cause cancer? Why is this important?
Cervical: HPV
Liver: Hepatitis
Burkitts lymphoma: EBV
Gastric Carcinoma: H. pylori
Can create vaccines to these viruses to basically create a vaccine to those cancers!
What can TAA’s be?
Viral proteins
Mutant cellular gene products
A normal protein that is being abnormally expressed
What is an oncofetal Ag?
A protein that is normal during development but NOT normal in adults.
Ex: Colon cancer has carcinoembryonic antigen (CEA)
What might the immune system use to kill cancer cells?
Cytotoxic T-cells (CD8+) Th1 Cells (CD4+) Natural Killer Cells Macs and Neutrophils Antibody Complement
How are cytotoxic T-cells used? How does the tumor fight back?
CD8 cells recognize TAA presented by MHC Class I.
CTL kill tumor via apoptosis or FAS
BUT tumors secrete PD-1 ligands that suppress CTLs
How are Th1 cells used? How does the tumor fight back?
CD4 cells recognize TAA, secrete lymphokines, and attract M1s. This could be a good treatment!
BUT tumors can help convert M1s to M2s…which can actually help the tumor grow.
How are Th1 cells used? How does the tumor fight back?
CD4 cells recognize TAA, secrete lymphokines, and attract M1s. This could be a good treatment!
BUT tumors can help convert M1s to M2s…which can actually help the tumor grow.
How are natural killer cells used? How does the tumor fight back?
This is innate immunity!
If an Ab has been creased to the TAA, then ADCC can be used to kill the cell.
NKs can see even the tumor cells that have down-regulated MHC (huge advantage over T-cells!) –> they are able to detect stress proteins.
NKs also stimulate CD4 cells for additional attack.
How are Macrophages and neutrophils used? How does the tumor fight back?
Macs and neutrophils are activated via foreign products….
BUT if they become M2s, can aid the tumor!
How are antibody and complement used? How does the tumor fight back?
Not used very well for treatment directly, but are good for diagnosis.
Can couple an injected Ab to radiation, toxins, etc.
What happens if the above lymphocytes are able to infiltrate the tumor?
These are Tumor Infiltrating Lymphocytes (TILs!)
These kill the tumor very well, and can be used for customized tumor treatment via adoptive cell transfer.
If a patient has TILs, they have a better prognosis.
What is adoptive cell transfer?
Use a T-cell from inside a tumor to expand and create “primed cells” that are tumor-specific (specific to the tumor and the patient)
Inject these T-cells into the tumor for directed attack
But…doesn’t work very well because of a mysterious blocking factor
What is the main finding of the Hellstrom Experiments?
All patients with a working immune system have T-cells that can kill the tumor.
Patients that have progressive tumors have something in their serum that inhibits the T-cells from doing their job.
Patients that have regressive tumors do not have that blocking factor, thus the immune system is effective against tumors.
What are 4 types of immunotherapy?
- Specific Immunization (A tumor vaccine)
- Innocent bystander killing
- Use an Ab to the TAA’s (use MAbs)
- Use adoptive cell transfer therapy
