Cancer Flashcards
Define cancer
A group of diseases characterized by:
- Uncontrolled cell growth
- Invasion of cells into surrounding tissue
- Metastasis
What causes cancer ?
- genetic mutations
- chemical carcinogens
- radiation
- viral/ bacterial infections
How do genetic mutations cause cancer ? (3)
- inactivation of tumor suppressors (the brakes)
- alteration of DNA repair gene function (the mechanic)
- over expression of oncogenes (the gas pedal)
NOTE: normal cells have a balance of growth of promoting and suppressing signals
T or F: the presence of tumor-associated macrophages in a tumor is associated with a worse prognosis
TRUE; the presence of tumor-associated macrophages in a tumor is associated with a worse prognosis
Can cancer cells from one mouse grow in another syngeneic mouse ?
Yes, tumor will grow in a syngeneic host because it will not be recognized as foreign
Can immunocompromised mice without a thymus still destroy foreign cancer cells ?
Yes, NK cells and macrophages are still intact
- they are not more susceptible to tumor formation
TILs and prognosis
- More Tumor-Infiltrating Lymphocytes in a tumor indicates a better prognosis
- TILs can fight cancer for longer
TSAs vs TAAs
Tumor Specific Antigens:
- specific to tumor
- new protein structure due to genetic mutations
Tumor Associated Antigens:
- normal proteins, not limited to tumor
- incomplete tolerance by immune system (towards overexpressed proteins, embryonic proteins*)
*NOTE: only expressed during fetal development)
Example of a TSA
BCRL-ABL fusion gene = Philadelphia chromosome
Examples of a TAA
HER2 overexpression
Evidence for TAA recognition
Melanoma Vitiligo
- immune system attacks cancer cells but also kills off melanocytes (normal and abnormal) = patchy skin color
WIP How does immune system respond to cancer ?
- Tumor cell invasion = inflammatory response
- Innate immune system attacks tumor mass via infiltrating
lymphocytes (NK cells, γδ T cells) - Release IFN-γ cytokine (Cytostatic, Pro-apoptotic) = chemokines production (angiostatin, recruits more NK)
- Tumor cell death
- Dendritic cells (ingest cell debris + transports to lymph node)
- NK cells (release IFN-y) and macrophages (release IL-12) activate each other
What is the equilibrium phase of immune system against cancer ?
- elimination is not complete
- selection pressure* on tumor by lymphocytes and IFN-y
= tumor cells develop immunological resistance - can last for years
*NOTE: cancer cells that resist immune attacks (by changing surface markers or by secreting immunosuppressive factors) have a survival advantage. Over time, the tumor population may evolve to favor cells that are less visible to the immune system or capable of inhibiting immune responses, such as through the downregulation of MHC
What is the escape phase of immune system against cancer ?
- “Immunoevasion”
- growth = takes years to develop a clinically apparent tumor
Immunoevasion Strategies of cancer
- hides identity
- avoid apoptosis
- induces immunocyte apoptosis
- neutralize complement
- inactivate immunocytes
How do cancer cells hide their identity ? (2)
- destroys MHC I of CD8+ T killer cells
- stop displaying TAA or TSA
How do cancer cells prevent apoptosis ?
- only suppresses 1/6 of MHC I to prevent NK killing
- decrease CD80/86 co-stimulation during T cell activation
- cancer cells release own soluble FasL to cause T cell apoptosis
How do cancer cells neutralize complement ?
cancer cells over express CD59 = prevents complement binding
How do cancer cells inactivate immunocytes ?
- inhibit or kill T cells (cancer cells can express own CD40L)
- attract T reg cells to site (CCL22) = T reg suppresses T cytotoxic and T helper cells = calms down immune response
