Tumors Flashcards
(23 cards)
malignant transformation:
when a cell has become able to form a cancer, it is said to have undergone malignant transformation
metastasis:
spreading of cancer cells thru the lymph or bloodstream to distant parts of the body other than the original site
proto-oncogenes:
genes that normally contribute positively to the initiation and execution of cell division
oncogenes:
mutant forms of proto-oncogenes that contribute to malignant transformation
mutagens:
a chemical or physical agent that increases mutation rate
carcinogens:
a mutagen that increases the risk of cancer cell formation
How does cancer arise?
from a single cell that has accumulated multiple mutations in genes that are involved in cell multiplication and cell survival
there are two types of genes that if mutated or mis-expressed can contribute to malignant transformation. name them
- proto-oncogenes: normally function in either initiation or execution of cell division
- tumor suppressor genes: these are genes that normally function to prevent unwanted proliferation of cells
chemical carcinogens typically give rise to what type of mutations?
give rise to single base change mutations
How can viruses cause cancer?
human oncoviruses infect cells and begin to express virally encoded proteins that can over-ride the cell’s normal mechanisms for regulating cell division
some viruses prevent the normal tumor suppression mechanisms of infected cells from operating; gives rise to abnormally-proliferating cells
many tumor cells can be easily recognized and killed by what?
allogeneic CD8 T cells
if a tumor cell from one strain of mice is injected into a mouse of a different strain, the tumor cells can be killed (much like a transplant rejection). what does this show?
tumor cells can be recognized by immune effector cells
What is the difference in tumor specific antigens and tumor associated antigens?
antigens present on tumor cells but not on normal cells are referred to as tumor- specific antigens
antigens that are found on tumor cells, but are also found on normal cells (often in smaller amounts) are termed tumor-associated antigens
What is the most common tumor antigens?
peptides bound to MHC class I molecules;
recognized by CD8+ T cells
What are the surface determinants on tumor cells for?
recognized by antibody molecules (and B cell receptors)
What experiment proves that the immune system can kill tumor cells if a tumor immune response can be generated?
mice can be effectively immunized by injecting irradiated tumor cells;
an anti-tumor immune response is produced that can prevent subsequent transfer of live tumor cells of the same type
WRT HLA expression, how can tumor cells escape the immune response?
between 1/3 and 1/2 of the cells in a tumor have defects in expression of one or more of their HLA molecules (MHC class I molecules)
selective pressure for cells that do not present tumor antigens on their surface, and therefore cannot be recognized by CTLs
tumor cells that do not express MHC class I cannot be recognized by effector CTLs. how are they killed?
killed by NK cells
some tumors actually create a zone of immunosuppression around the borders of the tumor. How?
by producing cytokines that suppress or mis-direct immune responses
How are monoclonal Abs used in tumor recognization and therapy?
tumor-specific mAbs can be used to detect tumors
tumor-specific mAbs can also be used to target tumor cells for destruction
mAbs conjugated to a toxin molecule can be injected into a patient. When the MAb:toxin conjugate binds to a tumor cell, the toxin molecule can be taken up by the cell and the cell is poisoned from the inside
What is a drawback to monoclonal Ab treatments?
immune system will produce acquired immune responses specific for the foreign antibodies;
no further treatments with that antibody can be performed successfully.
BOOSTING T CELL RESPONSES IS ANOTHER APPROACH TO IMMUNOTHERAPY. How is this done?
if T cells specific for tumor antigens can be isolated from a patient, they can be grown and expanded in vitro
this expanded population of effector T cells can then be injected back into the patient
a recombinant DNA approach that has promise is to transfect tumor cells with cytokines or chemokines that either stimulate or chemattract dendritic cells to the tumor. What does this do?
this facilitates uptake and eventual presentation of tumor-specific antigens to naïve T cells