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32 Cards in this Set
- Front
- Back
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Which division (innate, adaptive, or both) of the immune system is required for the detection and elimination of cancer? |
Both innate and adaptive |
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Does spontaneous regression of tumors occur? |
Yes (e.g. ~2% of melanomas regress without treatment) |
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What immune processes contribute to tumor regression? |
Infiltration of solid tumors with immune cells
Tumor-specific antibodies in the circulation |
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Who is at high risk for development of tumors? |
Young or old patients
Immunosuppressed patients |
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Which division of the immune system is most important for the elimination of tumors? |
Adaptive |
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How are tumors recognized by the immune system? |
Tumor cells present antigens on MHC class I and class II |
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Why don't immune cells recognize the majority of antigens presented by tumors? |
The immune system has been tolerized to those antigens |
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What are the two types of antigens recognized on tumor cells? |
Tumor-specific antigens (TSA)
Tumor-associated antigens (TAA) |
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Tumor-specific antigen (Definition) |
An antigen found only on tumor cells; a mutant peptide from a mutated cellular protein |
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Tumor-associated antigen (Definition) |
An antigen found on both tumor cells and normal cells; may be a re-expressed embryonic antigen or an over-expressed, low abundance self-protein |
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Immunotherapy (Definition) |
Therapy utilizing treatments that involve or capitalize on the immune system |
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What type/s of immunity is elicited by tumor antigens? |
Both cell-mediated with humoral immunity |
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What are two examples of tumor antigens that have epitopes recognized by both immune effector mechanisms (cell-mediated and humoral)? |
Tyrosinase
CEA |
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Which type of cancer typically expresses tyrosinase? |
Melanoma |
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How does the immune system recognize and respond to tumor antigens? (Steps) |
1) Inflammation and antigen capture by DCs at tumor site
2) DCs migrate to lymph nodes
3) Effector T and B cells are primed in the lymph nodes
4) Effector cells migrate to the tumor site
5) Effector cells deliver effector function |
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What are the specific immune mechanisms of tumor cell destruction? |
1) Complement-mediated lysis by specific antibody
2) Direct cytotoxicity by NK cells
3) Antibody-dependent cell cytotoxicity (ADCC)
4) Nonspecific cytotoxicity by activated macrophages
5) Tumor-specific cytotoxicity by cytotoxic T cells |
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Why are most tumor cells capable of escaping complement-mediated lysis? |
Tumor cells are eukaryotic cells, so they express regulatory proteins (like CD59) that prevent assembly of the MAC |
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Why do cancers progress and kill a host with an intact immune response? |
Tumor cells have a "drive to survive" (mechanisms to evade immune recognition and elimination) |
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What two things do tumors rely on for success? |
1) Vascularization
2) Evading the immune response |
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What factor, released by tumor and host cells (macrophages), mediates the induction of angiogenesis? |
VEGF |
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What mechanisms allow tumors to evade immune recognition? |
1) Down-regulate MHC class I antigens
2) Down-regulate tumor-associated antigens (TAAs)
3) Release suppressive factors (TGF-β) or induce the host to release suppressive factors OR attract and stimulate the generation of Tregs and myeolid-derived suppressor cells (MDSCs)
4) Lower immunogenicity (no peptide:MHC ligand, adhesion molecules, or co-stimulatory molecules)
5) Tolerization of T cells via presentation of tumor antigens by APCs in absence of co-stimulaton
6) Antigenic modulation - antibodies against tumor antigens trigger endocytosis and degradation of the antigen
7) Tumor-induced privileged site (physical barrier to the immune system created by secreted factors) |
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How do the hypoxic conditions of a tumor cell contribute to evasion of immune recognition? |
Hypoxic conditions cause macrophages to release certain factors (e.g. immunosuppressive factors), creating a pro-tumor environment |
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Immunoediting (Definition) |
A dynamic process of immunosurveillance and tumor progression |
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What are the three phases of immunoediting? |
Elimination
Equilibrium
Escape |
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Why is immunotherapy a promising area of research for cancer treatment? |
The specificity of immune reagents (such as tumor specific T cells) can target tumor and ignore normal cells |
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What type of immunotherapy can generate memory and prevent tumor recurrence? |
Active immunization (tumor vaccines) |
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What type of immunotherapy does not require the host to generate antibodies? |
Passive immunotherapy (injection of monoclonal antibodies) |
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What are the steps involved in autologous T cell immunotherapy? |
1) Excise tumor
2) Enzymatically digest tumor
3) Plate tumor fragments
4) Culture with IL-2 to grow lymphocytes
5) Select tumor-specific lymphocytes
6) Expand to 10¹⁰ cells
7) Re-infuse post-lymphodepletion (chemotherapy, etc.) |
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What genetic modifications of tumor cells are being investigated as potential cancer treatments? |
1) Insertion of a co-stimulator gene
2) Insertion of a cytokine gene to attract dendritic cells |
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How is an autologous DC vaccine generated and used? |
1) Harvest CD14⁺ DC precursor
2) Culture with GMCSF and IL-4
3) Introduce tumor antigen to cultured DCs
4) Inject cultured DCs into patient
5) Injected DCs migrate to patient's lymph nodes, where an immune response is generated |
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What two immunotherapy approaches have been recently approved by the FDA? |
Provenge (DC vaccine)
Ipilmumab (Anti-CTLA-4 monoclonal antibody) |
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What is CTLA-4? |
A cell surface molecule that usually turns off T cells |
