Test 2: Tumor/Cancer Immunity Flashcards
Where are tumors most common?
tissues with actively dividing cells
What some viruses that encode proteins (oncogenes) directly inducing tumor development?
- Human papillomavirus (oral cancers),
- Human t-lymphocyte virus (retroviruses RNA),
- Epstein Barr virus,
- Human herpes virus 8
How does the immune system involved in inflammation of cancers?
chronic unresolved inflammation can promote tumor development so immune system tries to prevent this by effectively elimination of pathogens and resolution of inflammation
What is Immune Surveillance Theory?
immune system identifies and eliminates early stages of can car before it has the chance to grow
- highly controversial
In studies of Rag/IFNy knock out mice without functional T, B, and NK cells, what happened and what does this suggest?
spontaneous development of non-viral induced tumors and are much more susceptible to carcinogen-induced tumors proven that cells of the immune system work together to protect against tumors
Tumors are weakly immunogenic because…
they’re derived from host cells
What are some reasons in why immune system fails to prevent growth of tumors?
- tumors derived from host cells
- rapid growth/spread of tumors
- tumors have specialized mechanisms for evading host immune responses
What are the immune response to tumors?
- cytotoxic CD8 T cells: principal mechanism
- CD4 T cells: provide cytokine-mediated help to CD8 cells
- antibodies: via complement activation with macrophages or NK cells (still unsure if this is effective in killing tumors)
- NK cells: attack cells with decreased/low class I
- Classical (M1) macrophages: cluster around tumors and kill tumor cells more effectively than normal cells
Alternate (M2) macrophages can also be induced but actually enhance tumor progression
How do Cytotoxic T cells respond against tumors?
- DC cells phagocytose tumor cells
- go into lymph
- activate CD8 T cells
- leave through circulation to tumor cells and kill them
Why are tumors good invaders of immune system?
- some tumors lack distinctive antigenic peptides
- tumor cells are poor antigen presenting cells because: lose antigens spontaneously and class I molecules, lack adhesion molecules, and do not express costimulatory or MHC class II molecules
- tumors can induce inhibitory immune cells (M2 macrophages)
- tumors can secrete immunosuppressive factors
- tumors can impair or inhibit NK cells
- tumor specific blocking antibodies
- tumor express high levels of gylcocalyx molecules that can hide surface antigens
How does monoclonal antibody immunotherapy work?
- act by immune mediated mechanisms or through interference with tumor growth
- done by anti-tumor activity or radioactive isotopes/toxic chemical to deliver cytotoxic therapy directly to tumors
How does immune adjuvants immunotherapy work?
- Bacilli Calmette-Guerin injection into bladder after resecting tumor which is more effective than chemo
- Toll-like receptor agonist which is effective against HPV induced warts and low grade epithelial tumors
How does cytokine immunotherapy work?
- IL-2 and IFNa
- TNF
low response and toxic
How does prophylactic immunotherapy work?
- vaccines against oncogene and non-oncogenes
- antibiotic tx to eliminate cancer causing microorganisms before cancer develops or during early cancer development
How does bone marrow transplantation immunotherapy work?
- bone marrow ablative therapy followed by allogenic bone marrow transplantation to kill off leukemia cells and give bone marrow that will kill those cancer cells
What are current clinical trials for immunotherapies?
- development of agonist monoclonal antibodies against co-stimulatory molecules expressed by T cells
- development of antigen-specific vaccines (mixed with adjuvant in some trials)
- immunization with professional antigen presenting cells (DC)
What is Provenge?
- first FDA approved therapeutic vaccine for prostate cancer
- take APC (DC) and culture them with a fusion and inject them to cause DC to become activated and develop capacity to present antigen to CD8 cells
What is adoptive cellular therapy?
- take patients own lymphocytes, culture with IL-2, and inject back into patient to try to get tumor regression
Why aren’t immunotherapies not as effective as we thought?
negative regulators of immune response interfere with induction of tumor immunity
What are CD4CD25 regularly T cells found in?
- found in late stage ovarian cancer showing that these cells are interfering with anti-tumor T cell responses (hurting us more when cancer is present)
What are newer strategies in response to controlling negative regulators for cancer?
- downregulation/elimination of regulatory T cells (CD4CD25)
- inhibiton of negative signaling
What does Ipilimumab do?
blocks negative signaling from CTLA-4 so CTLA-4 won’t bind to B7 and the T cell can be activated and used to treat tumors
antagonist
What does Nivolumab do?
block negative signaling from PD-1
because tumor cells express PDL-1 which inhibit CD8 cells so this will block PD-1 and PDL-1 so the CD8 cells are capable of killing the tumor cells
antagonist
