Term
| Cancer: Epithelial cells give rise to ____. |
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Definition
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Term
| Cancer: Mesenchymal connective tissues give rise to ___. |
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Definition
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Term
| Cancer: Hematopoeitic cells give rise to ___ and ___. |
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Definition
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Term
| What are some causes of malignant transformation? |
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Definition
irradiation (UV light)
exposure to chemical carcinogens
oncogenic viruses (ex: HPV)
chronic inflammation |
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Term
| There is a strong linkage between chronic inflammation caused by __ ___ ___ and the development of esophageal carcinomas |
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Definition
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Term
| What type of cancer has inflammatory bowel disease been linked to? |
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Definition
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Term
| What happens in metastasis? |
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Definition
- a matrix of metalloproteinases produced by a tutor (and host cells) degrade the extracellular matrix components
- Then the tumour elaborates factors that stimulate new blood vessel development
- the malignant tumour metastasizes |
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Term
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Definition
| the elaboration by tumours to stimulate new blood vessel development so that the tumour can be fed |
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Term
| Cancer stem cells are __-resistant and __-resistant |
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Definition
| - they are chemoresistant and radioresistant |
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Term
| What is immune surveillance? |
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Definition
| a function of the immune system --> destroy transformed cells before they become tumours |
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Term
| How is the immune system able to do immune surveillance (how does it recognize "transformed" cells vs normal cells)? |
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Definition
| cancer cells express antigens on their surface that are not found on normal cells |
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Term
| What evidence is there that the immune system responds to cancer? |
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Definition
1) Occasionally, people can have spontaneous tumour regressions (if immunocompetent). There is an increased incidence of cancer in immunocompromised patients
2) Mice w/ immunological defects have greater susceptibility to spontaneous or induced tumours (even some that other animals reject)
3) Immune cells (including T cells) accumulate at the tumour site (indicating that there is tumour recognition by the immune system)
4) Tumour-reactive T lymphocytes (CD4+ and CD8+) and antibodies can be detected in the peripheral blood of many cancer patients |
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Term
| What evidence complicates the issue of immune surveillance? |
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Definition
1) Immunosuppressed patients don't get more common tumours (breast cancer or prostate)... they tend to get more virally induced cancers
2) Immune cells may arrive at the site of the tumour to help (dun dun dunnnn!!!) --> macrophages may play a role in metastasis where mast cells may contribute to neoangiogenesis
3) It is difficult to characterize antigens that are specific to tumour antigens (know PSA is specific to the prostate but not to prostate cancer) |
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Term
| When heat shock proteins (DAMPs) are released by dying tumour cells, what type of signal do they send? |
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Definition
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Term
| What releases HMGB1 (a DAMP)? |
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Definition
| Necrotic tumour cells --> as the tumour expands, the central part of the tumour has trouble getting oxygen... they die and send out this danger signal to notify |
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Term
| What are tumour-specific antigens? |
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Definition
- antigens that aren't on normal cells (only transformed ones)
(note: many are restricted to a certain type of cancer) |
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Term
| What are tumour-associated antigens? |
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Definition
| - the abnormal expression of normal protein |
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Term
| How are tumour-specific antigens induced? |
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Definition
| - infection with oncogenic viruses or exposure of the cells to mutagenic agents |
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Term
| What process can also result in an abnormal repertoire of peptides that act as tumour-specific antigens? |
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Definition
| post-translational modification of normal protein |
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Term
| Tumour-associated antigens may be ___ proteins expressed on healthy cells but __-____ on tumour cells |
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Definition
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Term
| What are oncofetal antigens? |
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Definition
| tumour-assciated antigens that may be expressed on fetal tissues, but not on normal adult tissues |
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Term
| What cells are bigger? Tumour cells or lymphocytes? |
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Definition
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Term
| Describe the steps involved in the antibody response to TSA/TAA antigens |
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Definition
1. dendritic cells take up tumour proteins and present TSA and/or TAA-derived peptides on MHC class II molecules
2. The dendritic cells induce tumour-specific CD4+ cells
3. Antibody binds to TSA/TAA antigens on the surface and induces complement mediated lysis |
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Term
| Describe the FasL part of tumour-associated immune suppression. |
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Definition
Tumour cells have soluble and/or membrane-bound FasL
-When the CD8+ T cells come in, ready to kill, the tumour cells bind Fas on the surface of the CD8+ T cell and kill them instead! |
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Term
Tumour cells elaborate ____ cytokines.
Give examples: |
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Definition
immunosuppressive
TGF- beta
IL-4, -6 and -10 |
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Term
| Why do tumour cells express less class I MHC? (at a basic level) |
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Definition
| Their primary goal is to divide - so they turn off things that won't help in that goal |
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Term
| What does the loss of class I MHC expression on cancer cells prevent? |
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Definition
Class I presentation of TSA/TAA to CD8+ T cells
So this protects the cancer cells from CTL killing of tumour cells |
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Term
| What type of cells to natural killer cells recognize? |
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Definition
| cells with no (or low) Class I MHC |
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Term
| How do macrophages help tumours? |
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Definition
- Tumours secrete cytokines that cause macrophages to come to the periphery of the tumour
- once there, they secrete proteases which degrade and allow for metastasis
They also help with neoangiogenesis |
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