Final Exam (Lecture 22) - Tumor Immunology

Question 1

List at least two general categories of tumor antigens.

Answer 1

1) Mutated proteins

2) Viral antigens

Question 2

Describe the important innate and adaptive cellular immune response to tumor cells, how they recognize the tumor cell, and how they contribute to tumor cell death.

Answer 2

1) Innate:
- NK cells:
- Recognize the decrease in MHC I
expression, stress proteins, and antibody on
damaged/infected cell
- Kill via: apoptosis (TNF and INF-gamma,
CD95/CD95L, perforin/granzyme

  - M1 macrophages: Activated by INF-gamma
  - Kill via: cytokines, TNF, lysosomal enzymes, 
    nitric oxide and oxygen radicals

2) Adaptive:
- CTL:
- Recognize abnormal cellular protein,
excessive amount of self peptide or viral
peptide on MHC I
- Kill via: same as NK cells

  - TH1 Cells: 
  - Recognize peptide on MHC II
  - Kill via: Secretion of cytokines to activate CTLs
    NK cells, and M1 macrophages

  - Antibodies:
  - Recognize tumor antigens
  - Kill via: Marks cell for death

Question 3

List at least two ways tumor cells evade being detected by the immune system.

Answer 3

1) Low or lack of expression of MHC I

2) Production of immunosuppressive cytokines

Question 4

Describe one type of immunotherapy used to treat cancer (other than vaccine).

Answer 4

Chimeric Antigen Receptors:
- Recombinant and receptors for specific
tumor antigens chimerized with special
signaling tail and transferred to T cells

   - When they bind to tumor antigen, signals the
     killing mechanism of the T cells

Question 5

Explain how the canine melanoma vaccine works; including the type of tumor antigen targeted, the type of vaccine, and how it works to destroy the tumor.

Answer 5

Target: Tyrosinase

Type of vaccine: DNA vaccine that codes for
human tyrosinase

How it works:
1) Tyrosinase gene placed in bacterial plasmid
2) Injected intradermally or intramuscularly
3) Plasmid taken up by dendritic cells
4) Tyrosinase proteins are made and
presented on MHC I and MHC II
5) CTL and TH1 recognize human tyrosinase as
foreign and B cells recognize some that are
released
6) Dog responds to human tyrosinase and
clonally expands and cross reacts to
recognize canine tyrosinase breaking
tolerance

Question 6

In what ways are NK cells and CD8+ CTLs similar in the way they recognize and remove neoplastic cells? Different?

Answer 6

Similar:
- Both kill via apoptosis with perforin
and granzyme

Different:
- NK cells:
- Recognize stress proteins and
- Decreased MHC I expression

  - CTLs:
      - Has to see protein processed and
        presented on MHC I molecule

Question 7

What general process if crucial for the development of CTLs against tumors?

Answer 7

The tumor cells need to present proteins on MHC I through endogenous pathway.

Question 8

How are checkpoint blockade mAbs (monoclonal antibodies) and anti-tumor antibodies different? Similar? Think of the goals of each therapy.

Answer 8

Similar:
- Both trigger CTLs to kill tumor cells

Different:
- Anti-tumor antibodies:
- Specific to the tumor

  - Checkpoint Blockade:
     - Non-specific immune stimulation

Question 9

Are cancer vaccines treatments or preventatives?

Answer 9

Treatments