Tumor Immunology Flashcards
What causes cancer ?
cancer arises from a single cell that has accumulated multiple mutations in genes that are involved in cell multiplication and cell survival
What two types of genes lead to malignant transformation ?
- proto-oncogenes: normally function in either initiation or execution of cell division 2. tumor suppressor genes: these are genes that normally function to prevent unwanted
proliferation of cells
Why doesn’t cancer happen all the time ?
it has been estimated that a cell must acquire 5-6 different mutations in order for it to become a cancer cell (seeIS3-Figure 16.3)
•• due to low mutation frequency and this requirement for multiple mutations, formation of cancer cells does not usually occur at a high rate; therefore, the incidence of cancer increases with age, and cancer is generally considered a disease of the elderly
What are the environmental factors that increase mutation rate ?
• there are chemical and physical agents known as mutagens that increase rate of mutation •• any mutagen that increases the risk of cancer is known as a carcinogen
What type of people are at a high risk of developing cancer?
• people that have prolonged are heavy exposure to carcinogenic agents are at higher risk of developing cancer
•• chemical carcinogens typically give rise to single base change mutations
•• radiation tends to induce more pronounced mutations (DNA breaks, cross-linked
nucleotides, abnormal recombination, etc.)
Do viral pathogens cause the development of cancer cells ?
ome viral pathogens can cause development of cancer cells
•• 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
What immune cells target cancer cells ?
many tumor cells can be easily recognized and killed by 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); this showed that tumor cells can be recognized by immune effector cells
Why dont all cancers get eliminated by the immune system ?
- most cancers are not eliminated by the immune system, but this is probably due to the inability of the immune system to recognize the tumor cells as non-self
- • the mutations that arise in a cell leading it to become a tumor cell typically result in only small changes that go unrecognized by the immune system. Over time, as the cancer cell proliferates (and therefore, the mutation rate increases), additional mutations accumulate, and eventually, new antigens are produced by the tumor cell (tumor antigens)
What are tumor 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 MHC are tumor antigens presented on ?
• the most common tumor antigens appear to be peptides bound to MHC class I molecules; recognized by CD8+ T cells
Can tumor cells be recognized by B cells
tumors also typically have surface determinants that can be recognized by antibody molecules (and B cell receptors)
How can the body detect tumor cells that do not express MHC-1 ?
tumor cells that do not express MHC class I cannot be recognized by effector CTLs; however, they can be killed by NK cells (see JW7-Figure 15.16); unfortunately, only cells that are devoid of production of each of the MHC class I alleles is susceptible to NK cell-mediated killing
Can monoclonail antibodies specific for a tumor be synthesized and expressed?
when a tumor is characterized to the point that a unique tumor antigen has been identified, monoclonal antibodies specific for that tumor antigen can be produced
•• tumor-specific mAbs can be used to detect •• tumor-specific mAbs can also be used to target tumor cells for destruction
Can recombinant cytokines be used to treat proliferating tumor cells ?
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; this facilitates uptake and eventual presentation of tumor-specific antigens to naïve T cells
To evade the immune response can tumor cells induce immunosupression ?
some tumors actually create a zone of immunosuppression around the borders of the tumor by producing cytokines that suppress or mis-direct immune responses
