Tumor immunology

Question 1

What are carcinomas?

Answer 1

Turmors that arise from epithelial cells and are the most common of cancers

Question 2

What are sarcomas?

Answer 2

Tumors that originate in muscle cells, fat cells or fibroblasts

Question 3

What are lymphomas?

Answer 3

solid tumors of lymphoid tissues

Question 4

What are leukemias?

Answer 4

Tumors derived from lymphocytes and other hematopoietic cells

Question 5

What are the characteristics of benign tumors?

Answer 5

relatively slow growth rate, consist of somewhat differentiated cells and usually become encapsulated by connective tissue, therefore they don’t spread to other body sites

Question 6

When are benign tumors fatal?

Answer 6

They are not usually fatal unless they occur at critical sites such as the brain or heart.

Question 7

What are the characteristics of malignant tumors?

Answer 7

consist of undifferentiated cells and readily metastasize. Cancer is usually fatal if untreated

Question 8

What are tumor specific antigens? How do they arise?

Answer 8

antigens that are unique to a particular tumor and are not present on normal cell types. They arise as a result of point mutations or gene rearrangements that occur during oncogenesis.

Question 9

Why aren’t TSAs used for drug therapy?

Answer 9

not commonly seen in human tumors

Question 10

What are Tumor-associated antigens (TAA’s)?

Answer 10

antigens shared by different tumors and can also be found on normal tissues.

Question 11

What is the immunosurveillance theory?

Answer 11

Immune system detects and destroys CA (daily?)

Question 12

What are oncofetal antigens?

Answer 12

Antigens expressed on fetal, but not adult tissues

Question 13

What are alpha fetal proteins?

Answer 13

Proteins produced by certain liver CAs, replaced by albumin in adult.

Question 14

What are carcinoembryonic antigens?

Answer 14

Antigens that are increased in colon CA and smoking

Question 15

What are tumor associated antigens useful for, if you cannot use them to target therapy?

Answer 15

Diagnostic and monitoring

Question 16

What are the three DNA viruses discussed in class that have been shown to induce tumors and express viral antigens on class I MHC proteins?

Answer 16

Epstein-barr causes B cell lymphoma

HPV-cervical carcinoma

Hep B-hepatocellular carcinoma

Question 17

What is the RNA virus discussed in class that can produce tumors?

Answer 17

The RNA virus human T lymphotropic virus-1 (HTLV-1) causes an adult T cell leukemia/lymphoma of CD4+ T cells.

Question 18

Why are tumors derived from viruses particularly immunogenic?

Answer 18

Seen as foreign

Question 19

What are differentiation antigens?

Answer 19

Tissue specific, or differentiation, antigens that are present on normal cells types of adults can be expressed by some tumor types that develop from a particular tissue

Question 20

When are differentiation antigens used?

Answer 20

diagnosing certain tumors by revealing their origin

Question 21

Why are tumors difficult for the immune system to respond to? (2)

Answer 21

Rarely cause inflammation

Don’t express unique antigens

Question 22

How can antibodies contribute to tumor cell proliferation?

Answer 22

Block receptor sites for CTLs

Question 23

True or false: antiboddy production has been demonstrated to inhibit tumor developement

Answer 23

False

Question 24

CTLs are produced against what types of CA? (3)

Answer 24

carcinomas and sarcomas as well as virus-induced tumors.

Question 25

What are tumor-infiltrating lymphoctytes largely composed of?

Answer 25

CTLs

Question 26

NK cells are better at lysing CA cells with what origin?

Answer 26

Of hematopoeitic or virus induced

Question 27

What is the mechaism that allows NK cells to attack tumor cells?

Answer 27

Downregulation of class I MHC

Question 28

What are the three chemicals that cause NK cells to become LAK cells?

Answer 28

Interferons, TNF-alpha, and IL-2

Question 29

How do macrophages attack tumor cells?

Answer 29

Release TNF-alpha which kills tumors, or attacks blood supply ADCC

Question 30

What are the tumor evasion strategies?

Answer 30

Down regulate MHC Induce tolerance of specific T cells d/t lack of inflammation

Question 31

How does the destruction of highly immunogenic tumor cells by the immune system lead to CA?

Answer 31

May just select out the easy ones and leave the less immunogenic CA

Question 32

Can CA cells outgrow the immune system?

Answer 32

Yes

Question 33

What can some antigens that are shed by tumor cells do?

Answer 33

bind to cell surface receptors of immune system cells and prevent proper function.

Question 34

What is the effect of mucoploysaccharides on tumor cells?

Answer 34

Tumor antigens may be masked by tumor cell mucopolysaccharides which prevent recognition by the immune system.

Question 35

What happens when TGF-beta is released by tumor cells?

Answer 35

Suppress immune system

Question 36

How can tumor cells become immunoprivielged sites?

Answer 36

Encase themselves in collagen and fibrin

Question 37

How does hyperthermia work to destroy tumors?

Answer 37

Superheat them

Question 38

How does radiotherapy work?

Answer 38

X-rays or colbalt 60 induces ionizing radiation to destroy rapidly dividing cells

Question 39

How does chemotherapy work?

Answer 39

Inhibits DNA replication, RNA transcription or protein syntehsis

Question 40

What are the three advantages of tumor immunotherapy?

Answer 40

1. Specificity to tumor cells 2. Fewer side effects 3. More effective

Question 41

How can one vaccinate against a tumor?

Answer 41

Increase immunogenicity of tumor antigens to get an immune response

Question 42

What are the MAGE antigens in melanoma prevention do?

Answer 42

Induce CTLs for melanoma

Question 43

Why is the hep B vaccine considered tumor prevention?

Answer 43

It decrease the incidence of hepatocellular carcinoma.

Question 44

What does Herceptin target?

Answer 44

HER-2/neu receptors of breast CA, to block ligand interaction

Question 45

What are immunoconjugates?

Answer 45

Antibodies coupled to a toxic substance

Question 46

What is the main issue with immunoconjugaes?

Answer 46

Cross reactivity

Question 47

What fragments of antibodies are used in immunoconjugates to avoid non-specific binding?

Answer 47

F(ab')2 (so no Fc binding)

Question 48

How are bi-specific antibodies used in immunoconjugate therapy?

Answer 48

binds tumor antigens to CTLs

Question 49

What is in vitro purging of bone marrow?

Answer 49

Freeing bone marrow from CA tumors via antibodies and complement to provide for bone marrow transplants

Question 50

What is LAK therapy?

Answer 50

Peripheral NK cells cultured in high dose IL-2 to stimulate LAK cells. Lak cells are tumoricidal

Question 51

What are the two CA types that LAK therapy has been effective in?

Answer 51

Renal cell carcinoma | Malignant melanoma

Question 52

What is tumor infiltrating lymphocyte (TIL) therapy?

Answer 52

Leukocytes from solid tumors cultured with IL-2 and given to pt, thus giving pt LAK cells and tumor specific CTLs

Question 53

What is cytokine therapy? Why is it not used more often?

Answer 53

IL-2 of INF-alpha is infused into patients to generate LAK cells and activate CTL's in vivo. Lots of side effects

Question 54

What is the effect of administering IFN-alpha to pts? (3)

Answer 54

antiproliferative effects on tumor cells, increases NK cell activity, and induces class I MHC expression on tumor cells to make the tumors more immunogenic.

Question 55

What is transfection of cyotokines genes into tumor cells?

Answer 55

Administering IL-2 or TNF directly to tumor cells via antibody targeting