Tumor immunology (Daemen)
21 important questions on Tumor immunology (Daemen)
What is the difference between benign and malignant tumors?
In malignant tumors the tumor cells do penetrate surrounding tissue (kwaadaardig)
Name five different types of cancers and their origin.
Sarcoma: derived from connective tissue. Bone, cartilage, fat nerve
Lymphoma and leukemia: from hematopoietic cells
Blastoma: from immature precursor cells or embryonic tissues, more common in children
Germ cell tumor: from pluripotent cells in testicle or ovary.
How does cancer develop?
Through micro-organisms such as bacteria, viruses and parasites.
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What percentage of cancers worldwide does infection plays a role?
Which cells play a role in the adaptive immune response against tumors?
CD4+ T helper cells (produce cytokines to stimulate CTL)
Also: antibodies
What is the mechanism behind NK cells to be activated or not against a tumor cell? (innate immunity)
ligand binds activating receptor (NK) V
MHC I binds inhibitory receptor (NK) V,
result: NK does not kill
ligand binds activating receptor (NK) V
no MHC I to bind inhibitory receptor (NK) X
result: NK kills
How do macrophages respond to tumor cells? (innate immunity)
What kind of different types (4) of tumor antigens do tumor cells express?
- Oncogene or mutated tumor suppressor gene
- Overexpressed or deflective expressed self protein
- Oncogenic viruses
How do T cells get activated and trafficked as a result of cancer antigens?
2) Cancer antigens presentation by dendritic cells/APC)
3) Priming and activation of T cells in lymph node
4) Trafficking of T cells to tumor (CTLs) through blood vessels
5) Infiltration of T cells into tumors
6) Recognition of cancer cells by T cells
7) Killing of cancer cells
For anti-tumor immunity, CTL requires cross-priming to become tumor-specific. What is this and what receptor and cytokines does this need?
The CD4+ T cell binds to the CD40 receptor on the APC which stimulates the CD4+ cell to express IL-2 which causes differentiation of tumor-specific CTLs.
What is perforin/granzyme-mediated cell killing by CTLs?
2) Granzymes (perforin and serglycin) enter the target cell cytosol and activate caspases.
3) Apoptosis of target cells.
What is Fas/FasL-mediated cell killing by CTLs?
Often the immune system fails and tumors can progress. Multiple co-stimulatory and inhibitory interactions regulate T cell responses.
Name 2 important inhibitory interactions and their compounds that take place in the lymph nodes.
CD80 or CD86 (APC) - CTLA4 (TC)
What is CTLA4 and what does it have to do with cancer development?
CTLA4 is expressed in regulatory T cells but only upregulated in conventional T cells after activation – a phenomenon which is particularly notable in cancers.
Tumor cells can evade immunization. For example by cancer cells growing faster than they're being killed. Name 4 other mechanisms.
2) NK cells have a limited capacity for clonal expansion
3) Immune suppressive factors and immunesuppressive cells decrease immune responses
- Treg cells
- myeloid-derived suppressor cells, MDSC
4) Inhibitory checkpoints like PD-1
Name the 3 types of passive immunotherapy
- anti-tumor antibodies
- suppression of the suppression
What are the effector mechanisms of tumor antibodies?
1) Interference with grow signal functions (for example Her2-Neu)
2) Complement activation (CDC)
3) Fcy-R-dependent lysis (ADCC, phagocytosis)
4) mAb-induced adaptive anti-tumor immune response
What does suppression of the suppression mean in passive immunization against tumor cells?
- Ipilimumab blocks negative signaling from CTLA4
- PD-L1/PD-1 blockades, blocks the inhibition of CTLs
What is active immunotherapy?
Induction of neutralizing antibodies against the structural proteins of the virus, for example the HPV- or HBV vaccine.
What is the B7 family?
What kind of therapeutic cancer vaccines are there?
- Purified tumor antigens
- APC-based vaccines
- Cytokine- and costimulator- enhanced vaccines
- DNA vaccines
- Viral vectors
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