Lecture 27; Therapeutic Immunology Flashcards
What is post transplant lymphoma?
- Cancer that arises in transplant patients because they are on immunosuppressants such as ciclosporin and methotrextate
What is the first step in treating post transplant lymphoma?
Reduce t cell immunsuppression
How does the cancer cause anti-tumor immune cell responses to fail?
- Lack of co-stimulation causes DC anergy
- Switches TH1 to TH2 TOLERANCE response
- MHC class one downregulation (genetic modifications do this i.e methylation or interrupted upregulation pathways i.e TAP)
What factors can Tumor cells release and what do they cause?
- TGFb = Inhibition of NK and CTL
- Factors that recruit Tregs and MDSC (myeloid derived supressive cells) = CD8 inhibition
What can NK cells release that fights tumors?
NK = HLA restricted
Release IFN;
- Increase MHC 1,2 expression = Increase adaptive response
- CD8 + Treg activation
- Blocks angiogenesis = restricts tumor growth
What can APC do in regarding to tumor cells?
APC can present apoptotic bodies derived from tumor cells
= Danger Signals
= Recognised by TLR
What cell is found to be increased in tumors?
Tregs increase in solid and blood tumors.
They release TNF(b) = TH2 or tolerance to tumor
(bad)
What are two old immunotherapy?
IL2 was given to boost T cell activaiton
BCG vaccination increase macrophage activity and was effective against bladder cancers
What are three effective immunotherapies looked at today?
Anti CCR4
Vaccination = CpG loaded cells
Regulatory blockade = Anti PD1
How are monoclonal antibodies used against cancer?
Monoclonal Antibodies
- Used to stimulate specific cells i.e B cells via CD20
- Herceptin (vaccination) tagers HEr2 nea on breast cancer cells
Describe the regulatory blockade using Anti-PD1;
Tumor PD1, down regulates T cell activity by interacting with PDL1 on T cells.
- Nivolumab is an IgG anti PD1 and blocks this interaction
- Effective for solid tumors
What does PDL1 actually do?
It is an apoptotic signal that would typically cause T cell apoptosis.
What are the three steps in producing an effective DC vaccination;
1) Optimally present relevant tumor antigens
2) Manipulate Immune Regulation to facilitate CTL response
3) Prevent CTL neutralisation at site of tumor antigens
= Cure
How can DCs be presented tumor antigens?
DCs can be fed tumor lysates or apoptotic bodies or specific tumor peptides
How are DC vaccinations increased in efficacy?
- Utilise a danger signal
- Adjuvants i.e GM CSF that enhance immune response
- Use other danger signals like tetanus toxin to enhance the humoral response.
