L13: Tumor Immunology

Question 1

Tumor types

Answer 1

1. ) Carcinomas: epithelial cells (most common CA)
2. ) Sarcomas: muscle cells, fat cells or fibroblasts
3. ) Lymphomas: solid tumors of lymphoid tissues
4. ) Leukemias: lymphocytes and other hematopoietic cells

Question 2

Characteristics of benign vs malignant tumors

Answer 2

1. ) Benign: slow growth, differentiated cells, usually encapsulated, not fatal unless at critical site
2. ) Malignant: undifferentiated cells, readily metastasize, usually fatal if untreated

Question 3

TSA vs TAAs

Answer 3

• TSA: tumor specific antigens (only on CA cells) – not common
• TAA: tumor associated antigens (also on normal tissues)

Question 4

Examples of TAAs

Answer 4

1. ) AFP: alpha fetal protein produced by certain liver CAs
2. ) Oncofetal antigens: expressed on fetal, but not adult tissues
3. ) CEA: carcinoembryonic antigen is high in colon CA and smokers

Question 5

Viral oncogenic antigens. Where are these presented?

Answer 5

1.) DNA viruses: EBV, HPV and HBV
2.) RNA viruses: HTLV (adult CD4+ T cell leukemia/lymphoma)
• presented on class I MHC

Question 6

Antigen(s) specific for B cell leukemias and lymphomas

Answer 6

• CD10 and immunoglobulin

Question 7

Antigen(s) specific for T cell leukemias and lymphomas

Answer 7

• IL-2 receptor (alpha chain), TCR, CD45R and CD4/8

Question 8

Antigen(s) specific for melanomas

Answer 8

• S-100

Question 9

Antigen(s) specific for carcinomas

Answer 9

• epithelial derived tissue, therefore cytokeratins

Question 10

Antibodies are the strongest form of immunity against tumors. True / False

Answer 10

• False, cell-mediated immunity is

Question 11

What type of tumors are CTLs produced against?

Answer 11

• Carcinomas, sarcomas and virus-induced tumors

Question 12

What are TIL’s?

Answer 12

• Tumor-infiltrating lymphocytes, which are mainly of CTL subtype that are found in solid tumors

Question 13

What type of tumors are NK cells produced against?

Answer 13

• Tumors of hematopoietic origin and virus-induced

Question 14

CTLs are the best defense against virus-induced tumors. True / False

Answer 14

• True. NK cells can also lyse these cells, but CTLs are the best

Question 15

Mechanism of NK cells destroying tumor cells

Answer 15

1. ) ADCC with some tumors (requires antibody)
2. ) Downregulation of class I MHC in some tumors (which normally acts as inhibitory signal)
3. ) LAK cells – subset of NK cells that are exposed to high levels of IL-2 and have T lymphocyte homology. They enhance killing of various tumor cells as well as recognize them better.

Question 16

What cytokines enhance NK cells in their lysis of tumor cells?

Answer 16

• TNF-alpha, IL-2

Question 17

Action of macrophage in killing tumor cells?

Answer 17

1. ) ADCC
2. ) Release of TNF-alpha (downstream effect on NK cells +…) directly lyses tumor cells (? Free radicals, hemorrhagic necrosis of tumor blood vessels?)

Question 18

How do tumor cells attempt to evade the immune system?

Answer 18

1. ) Lack of MHC expression (particularly class I)
2. ) Induce tolerance via absence of costimulatory molecules
3. ) Failure to produce tumor antigen
4. ) Anti-tumor abs acts as blocking factors
5. ) Antigen shed by tumor cells
6. ) Tumor antigens masked by mucopolysaccharides
7. ) Tumor releases immunosuppressive substances – TGF-beta
8. ) Creation of immunoprivileged site by encasement in collagen and fibrin

Question 19

Types of immunotherapies available against tumors

Answer 19

1. ) Tumor vaccines: vaccinate with tumor cells treated to increase immunogenicity or DCs loaded with tumor antigens. HBV vaccine decreases incidence of hepatocellular carcinoma
2. ) Antibody therapies: lysis by ADCC/complement, abs against growth factors (Her2-neu – herceptin)
3. ) Immunoconjugates: abs coupled to toxic substance directed towards tumor-specific antigen using Fab2 fragments
4. ) Bi-specific antibodies: genetically engineering abs that recognize tumor antigens and immune system cells
5. ) Purging bone marrow of tumor cells (autologous bone marrow transplantation in B cell lymphoma pts)
6. ) LAK cell therapy: NK cells cultured in high levels of IL-2 – differentiate into LAK cells then reinfused back into pt
7. ) TIL therapy: leukocytes from solid tumors cultured with IL-2 and given back to pt
8. ) Cytokine therapy
   a. ) IL-2: generates LAK cells, activates CTLs
   b. ) TNF-alpha: anti-tumor effects, but potential to develop septic shock
   c. ) IFN-alpha: increases NK cell activity and increases class I MHC expression on tumors
   d. ) Transfection of cytokine genes into pt tumor cells: immune stimulation locally instead of systemically

Question 20

A patient is diagnosed with diffuse large B cell lymphoma. A specific therapy was used that targeted the surface immunoglobulin that was expressed by his tumor cells. The tumor cell immunoglobulin is a type of \_\_\_\_\_\_\_ antigen.
1.differentiation
2.oncogenic viral
3.tumor-associated
4.tumor-specific
If an anti-idiotypic antibody was used to treat the lymphoma patient, it would recognize the \_\_\_\_\_ region of the tumor cell immunoglobulin?
1.Fab
2.Fc
3.Fc receptor
4.F(ab’)2

Answer 20

• tumor-specific

- Fab

Question 21

What is the most dreaded, yet all-to-common, outcome of the treatment of B cell lymphoma with anti-idiotypic antibodies?

1. Secondary tumors unrelated to the B cell lymphoma
2. Neutralizing antibodies against the therapy antibody
3. Tumor growth outpaces the amount of therapy antibody available
4. Tumor variants that don’t bind the therapy antibody

Answer 21

• 4.

Question 22

In an experimental attempt to treat a patient with disseminated colon cancer, cancer cells were transfected with a gene that increased the expression of class I MHC molecules. Which component of the immune response likely would participate in killing of the tumor cells?

1. Dendritic cells
2. Cytotoxic T cells
3. Macrophages
4. Natural killer cells

Answer 22

• 2.

Question 23

A patient had a particularly aggressive cancer. A sample of the patient’s tumor revealed that the cells produced a large amount of IL-10. This likely provided a fair degree of protection from the immune system by shifting the patient immune response toward a _____ type of response.

1. Th0
2. Th1
3. Th2
4. Th3
5. innate

Answer 23

• 2.