Test 2: Tumor/Cancer Immunity Flashcards

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1
Q

Where are tumors most common?

A

tissues with actively dividing cells

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2
Q

What some viruses that encode proteins (oncogenes) directly inducing tumor development?

A
  • Human papillomavirus (oral cancers),
  • Human t-lymphocyte virus (retroviruses RNA),
  • Epstein Barr virus,
  • Human herpes virus 8
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3
Q

How does the immune system involved in inflammation of cancers?

A

chronic unresolved inflammation can promote tumor development so immune system tries to prevent this by effectively elimination of pathogens and resolution of inflammation

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4
Q

What is Immune Surveillance Theory?

A

immune system identifies and eliminates early stages of can car before it has the chance to grow
- highly controversial

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5
Q

In studies of Rag/IFNy knock out mice without functional T, B, and NK cells, what happened and what does this suggest?

A

spontaneous development of non-viral induced tumors and are much more susceptible to carcinogen-induced tumors proven that cells of the immune system work together to protect against tumors

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6
Q

Tumors are weakly immunogenic because…

A

they’re derived from host cells

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7
Q

What are some reasons in why immune system fails to prevent growth of tumors?

A
  • tumors derived from host cells
  • rapid growth/spread of tumors
  • tumors have specialized mechanisms for evading host immune responses
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8
Q

What are the immune response to tumors?

A
  • cytotoxic CD8 T cells: principal mechanism
  • CD4 T cells: provide cytokine-mediated help to CD8 cells
  • antibodies: via complement activation with macrophages or NK cells (still unsure if this is effective in killing tumors)
  • NK cells: attack cells with decreased/low class I
  • Classical (M1) macrophages: cluster around tumors and kill tumor cells more effectively than normal cells
    Alternate (M2) macrophages can also be induced but actually enhance tumor progression
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9
Q

How do Cytotoxic T cells respond against tumors?

A
  • DC cells phagocytose tumor cells
  • go into lymph
  • activate CD8 T cells
  • leave through circulation to tumor cells and kill them
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10
Q

Why are tumors good invaders of immune system?

A
  • some tumors lack distinctive antigenic peptides
  • tumor cells are poor antigen presenting cells because: lose antigens spontaneously and class I molecules, lack adhesion molecules, and do not express costimulatory or MHC class II molecules
  • tumors can induce inhibitory immune cells (M2 macrophages)
  • tumors can secrete immunosuppressive factors
  • tumors can impair or inhibit NK cells
  • tumor specific blocking antibodies
  • tumor express high levels of gylcocalyx molecules that can hide surface antigens
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11
Q

How does monoclonal antibody immunotherapy work?

A
  • act by immune mediated mechanisms or through interference with tumor growth
  • done by anti-tumor activity or radioactive isotopes/toxic chemical to deliver cytotoxic therapy directly to tumors
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12
Q

How does immune adjuvants immunotherapy work?

A
  • Bacilli Calmette-Guerin injection into bladder after resecting tumor which is more effective than chemo
  • Toll-like receptor agonist which is effective against HPV induced warts and low grade epithelial tumors
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13
Q

How does cytokine immunotherapy work?

A
  • IL-2 and IFNa
  • TNF
    low response and toxic
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14
Q

How does prophylactic immunotherapy work?

A
  • vaccines against oncogene and non-oncogenes
  • antibiotic tx to eliminate cancer causing microorganisms before cancer develops or during early cancer development
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15
Q

How does bone marrow transplantation immunotherapy work?

A
  • bone marrow ablative therapy followed by allogenic bone marrow transplantation to kill off leukemia cells and give bone marrow that will kill those cancer cells
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16
Q

What are current clinical trials for immunotherapies?

A
  • development of agonist monoclonal antibodies against co-stimulatory molecules expressed by T cells
  • development of antigen-specific vaccines (mixed with adjuvant in some trials)
  • immunization with professional antigen presenting cells (DC)
17
Q

What is Provenge?

A
  • first FDA approved therapeutic vaccine for prostate cancer
  • take APC (DC) and culture them with a fusion and inject them to cause DC to become activated and develop capacity to present antigen to CD8 cells
18
Q

What is adoptive cellular therapy?

A
  • take patients own lymphocytes, culture with IL-2, and inject back into patient to try to get tumor regression
19
Q

Why aren’t immunotherapies not as effective as we thought?

A

negative regulators of immune response interfere with induction of tumor immunity

20
Q

What are CD4CD25 regularly T cells found in?

A
  • found in late stage ovarian cancer showing that these cells are interfering with anti-tumor T cell responses (hurting us more when cancer is present)
21
Q

What are newer strategies in response to controlling negative regulators for cancer?

A
  • downregulation/elimination of regulatory T cells (CD4CD25)
  • inhibiton of negative signaling
22
Q

What does Ipilimumab do?

A

blocks negative signaling from CTLA-4 so CTLA-4 won’t bind to B7 and the T cell can be activated and used to treat tumors
antagonist

23
Q

What does Nivolumab do?

A

block negative signaling from PD-1
because tumor cells express PDL-1 which inhibit CD8 cells so this will block PD-1 and PDL-1 so the CD8 cells are capable of killing the tumor cells
antagonist