Tumor immunology Flashcards
State the concept of the Immune Surveillance therory
Immunosurveillance Hypothesis: The immune system should be able to recognize and eliminate developing tumors based on recognition of neoantigens from the mutations of the transformation process.
The idea is that tumors are occurring to some extent all the time, but normally the immune system’s surveillance keeps the process under control
Discuss whether data from immunosuppressed and immunodeficient patients support the Immune Surveillance therory
- Evidence: virus-associated, and some non-virus-associated, tumors increase with immune suppression. Tumor-infiltrating Lymphocytes (TILs) are found in many tumors and seem to be acting to try and keep them in check.
- T cells, NK cells, and the innate immune system seem to be most central to this process.
immunoediting
immune system constantly ‘edits’ the body’s cells to eliminate anything that’s out of place. There are three main outcomes associated with this: elimination, equilibrium or escape
TSA:
tumor cell antigens not found on corresponding normal cells. Easier for the immune system to target.
TAA:
tumor cell antigens found on corresponding normal cells; they’re just more common on tumor cells. Harder for the immune system to target (it’s ‘self’ to T cells).
Viral tumor antigens:
generally TSAs (viral antigens not found in uninfected cells).
Mutant gene product antigens:
novel gene products made by tumor cells. Also generally TSAs since normal cells don’t make them.
Normal gene product antigens:
normal gene products made to excess by tumor cells. Generally TAAs since normal cells do make them, albeit at lower quantities. Types:
Oncofetal: antigens made in fetus but not in normal adult cells.
Differentiation: antigens involved in differentiation.
Oncospermatogonal/testis: antigens usually found only in germ cell development. Can be targeted well (since immune responses don’t generally travel into the testes).
Clonal: antigens only on the clone of cells that the tumor came from.
Define carcinoembryonic antigen (CEA) and discuss its usefulness in screening for, diagnosis and follow-up of colon cancer
The most familiar oncofetal antigen is carcinoembryonic antigen (CEA), found in the blood of patients with colon carcinoma and other cancers. The proper use of CEA measurement comes when you have a high index of suspicion of colon cancer; or, when such a cancer has been removed, to confirm complete excision (levels fall to 0 and remain there) or to warn of recurrence.
Role of CTL in killing tumor cells
CTL can recognize TAA presented by MHC class I. Naive T cells are activated in the lymph nodes, not at the tumor site, via interactions with antigen-presenting cells such as dendritic cells. Activated TAA-specific T cells leave the lymph node and migrate to the tumor. CTL can kill tumor cells by inducing apoptosis via either perforin or Fas-mediated pathways. The CTL also secrete IFN-gamma upon engagement of their TCR, which attracts and stimulates macrophages.
Role of NK in killing tumor cells
They recognize a small number of “stress-related” markers on tumor cells, using a small number of NK receptors which are neither immunoglobulin nor TCR.
-Here’s an interesting thing: NK cells are down-regulated if the target cell expresses Class I MHC. It’s like the body knows that if there’s a lot of Class I, that make a CTL target, so NK needn’t bother; but if the tumor decreases Class I, thinking to evade CTL, then it becomes a NK target
Describe the nature and therapeutic use of tumor-infiltrating lymphocytes, TIL, in adoptive cellular transfer therapy.
Cells directly from the tumor are called tumor-infiltrating lymphocytes (TIL). The T cells are expanded greatly in culture using cytokines such as IL-2. The patient’s immune system may then be partially destroyed by irradiation to make “room” for the expanded anti-tumor clones. They are reintroduced into the immune-depleted patient to kill remaining tumor cells
Describe a mechanism by which BCG treatment causes tumor regression
BCG: vaccine designed to prevent TB.
Injecting it straight into tumors can cause non-specific killing of tumor cells by T cells (nobody seems entirely sure why this is).
It also induces a delayed-hypersensitivity reaction to BCG (angry macrophages) which can engulf and destroy the surrounding tumor cells.
Discuss prospects and problems concerning the use of monoclonal antibodies in the diagnosis or treatment of cancer.
Prospects: Can use passive antibodies to target TAAs the body wouldn’t otherwise make antibody against. In the news lately: Herceptin (anti-HER2 surface growth stimulatory molecule) and antibodies against VEGF (angiogenesis factor).
Problems: The passive use of monoclonal antibodies against TAAs (like melanin) will probably affect normal cells expressing the TAA as well.
Discuss the principles underlying antibody or T cell methods that might be used as treatments of tumors
“the mechanisms used by T cells and antibodies that makes them effective in immunotherapies. For example, specific antibodies may kill the target cells by antibody-dependent cell-mediated cytotoxicity [NK cells–jcr], and specific CTL may be stimulated to kill the tumor using perforin, Fas, and TNF pathways when the patient is treated with specific vaccines (say antigenic peptide plus adjuvant [like the illicit help mechanism–jcr]).”
