Hudig: Tumor Immunology Flashcards
Are tumors considered self or non-self?
tumors are similar to self and have few antigens, so immune responses to tumors are limited
**don’t generate IL-1, TNFalpha, and signal 2
Give 3 reasons why immune responses to tumors are “weak.”
- tumor antigens are tolerated as self
- persistent immune responses lead to T cell exhaustion
- tumors create a suppressive environment
Tumorgenesis induces T cell (blank) – lack of inflammation and signal 2
anergy
What are the 3 E’s on tumor immunity?
elimination: immunosurveillance of highly antigenic neoplasms
equilibrium: tumor growth and immune killing both occur
escape: tumor loses antigens, secretes inhibitory factors, grows out of control, etc…
What phase is this: when tumors arise in the tissue, a number of immune cells can recognize and eliminate them
elimination phase
What phase is this: variant tumor cells arise that are more resistant to being killed; over time, a variety of different variants emerge
equilibrium phase
What phase is this: eventually, one variant may escape the killing mechanism or recruit regulatory cells to protect it and spread unchallenged
escape phase
Tumor immunity is usually (blank) for individual tumors
specific
What is the difference between tumor specific antigens and tumor associated antigens?
tumor specific antigens are found on tumors but not on normal cells (ex: papiloma viral ag’s in MHCI)
tumor associated antigens are found on both tumor and normal cells (ex: MAGE in melanoma or HER2 on breast cancer cells0
What are these: products of mutated oncogenes and tumor suppressor genes
tumor specific antigens
What are these examples of:
mutated p53 tumor suppressor protein
unique Ig receptors on B cell lymphomas
tumor specific antigens
What are these: over-expressed and abnormally expressed proteins
tumor associated antigens
Give some examples of tumor associated antigens
MAGE in melanoma (usu only expressed in the testis and placenta)
HER 2 in breast cancer (epidermal growth factor receptor)
EGFR is expressed at a higher level on cancer cells
5 antigens associated with myeloma
cyclin-dependent kinase 4 Beta-catenin MAGE1 Tyrosinase GP100/TRP2
This antigen is seen in squamous cell carcinoma
caspase 8
This antigen is seen in hepatoma
Alpha-fetoprotein
This antigen is seen in Burkitt’s lymphoma
EBV
Why are melanomas used for trials of anti-tumor immunity?
melanoma has 5 antigens, so it is easily recognizable
What are the 5 cell types active in tumor immunity
CD8 T cell (responds to tumor Ags in MHCIs)
TH1 T helper cells (to activate macrophages)
activated macrophages (to kill or increase cytokines)
NK cells (for immunosurveillance and to kill tumor cells if they’ve lost their MHC expression later)
T regs
What do NK cells do for tumors early on? Late in the game?
early: they are involved in immunosurveillance looking for whacky antigens
late: kill tumor cells if tumors lose MHCI
If an NK cell encounters a tumor cell that does not have MHCI molecules on it, it cannot stimulate a negative signal. So, what happens?
NK cell will become activated, release its contents and kill the cell
**On-off balance favors “off”. Lack of MHC means no more “off” so NK cell stays “on” and kills.
List three ways in which the tumor microenvironment reduces tumor immunity (killing of tumors)
- low immunogenicity (no peptide:MHC ligand, no co-stimulatory molecules on tumor cells)
- tumor is treated as self (tumor antigens are taken up and presented by APCs in absence of co-stimulation leading to tolerized T cells)
- tumors induce immune suppression by secreting factors like IL-10 and TGF-beta which inhibit T cells directly
What does CTLA-4 do for tumor cells?
it down-regulates T cell division
What can persistent antigen presentation by tumor cells do to CTL’s?
cause immune exhaustion
