2- Tumor Immunology

Question 1

cancer cells

general

Answer 1

lost normal reg control over growth so tissue destruct or host death
-comp for nutrients, obstruct vessels, inc suscept to infection

Question 2

tumor types

Answer 2

1. carcinomas- epi cells, most common
2. sarcomas- muscle, fat cells, fibros
3. lymphomas- solid of lymphoid tissue
4. leukemias- lymphs + hematopoietic cells

Question 3

bengin tumors

Answer 3

• slow growth rate (malig readily metastasize)
• somewhat differentiated (malignant is undiff)
• usually encapsulated so not spread
• not fatal unless @ critical sites

Question 4

tumor studies

Answer 4

1. immune resp to tumors
2. tumor antigens that induce immune resp
3. effector cells that kill tumor cells
4. immunologic methods to detect/dx/treat

Question 5

immunosurveillance theory

Answer 5

immune system detects/destroys cancer daily
-imp for tumors from viruses
-majority of cancers may be preventable

Question 6

tumor specific antigens

Answer 6

unique to particular tumor and NOT present of normal cell types
-from point muts or gene rearrange
-not common in human tumors
-immune resp targets may be altered self proteins

best option

Question 7

tumor associated antigens

Answer 7

antigens shared by diff tumors AND found on normal tissues so not good for therapy but good for detection/monitoring

i.e. oncofetal antigens, alpha fetal protein (liver cancer), carcinoembryonic antigen (colon cancer)

Question 8

oncogenic viral antigens

DNA

Answer 8

1. EBV = B cell lymphoomas
2. HPV = cervical carcinoma
3. HBV = hepatocellular carcinoma

relatively immunogenic bc seen as foreign

Question 9

oncogenic viral antigens

RNA

Answer 9

1. HTLV-1 = adult T cell leukemia/lymphoma with CD4+ cells

also relatively immunogenic bc foreign

Question 10

differentiation antigens

Answer 10

tissue specific antigens so aid in dx certain tumors/ reveal tissue of origin

i.e. CD10 for B cell tumors, CD4/8/TCR/IL-2 for T cell leukemias

Question 11

antibodies vs tumors

Answer 11

diff for immune sys to resp to spontaneous tumors bc rarely have inflamm (don’t elicit co stimulatory moles)
-tumors don’t express unique antigenic peptides

little evidence that natural antibodies inhib tumor growth

Question 12

cytotoxic T lymphocytes

CTLs

Answer 12

most effective vs virus induced tumors
-but also carcinomas, sarcomas

tumor infiltrating lymphocytes (TIL) in solid tumors made of anti-tumor CTL

Question 13

NK cells

Answer 13

hematopoietic tumors + virus induced
-act by downreg of class I MHC
-enhanced by interferons, TNF-a, IL-2

NK on steroids aka IL-2 = LAK cells for enhanced killing and broadened recognition

Question 14

macrophages

Answer 14

kill by ADCC or release of TNF-a
-TNF directly lyse tumor cells via free radicals or causing hemorrhagic necrosis of tumor blood vessels

Question 15

tumor evasion

Answer 15

1. not express MHC
2. MHC proteins can’t bind tumor antigen so no presentation
3. induce tolerance i.e. no costim molecules
4. antitumor Ab act as blocking factors
5. antigens shed by tumor bind cell surface receptors
6. tumor Ag masked by mucopolysaccs
7. immunosupp substances released (TGF-b)
8. create immunopriv site by encasing in collagen and fibrin

Question 16

cancer therapies

non immune

Answer 16

1. surgery- reduce tumor load and remove before meta, combo drugs + radiation
2. hyperthermia- destroy thru superheating body tissues
3. radiotherapy- x ray or cobalt 60, best on well defined non meta tumors
4. chemotherapy- inhib DNA, RNA, protein syn but immunosupp side effects fatal

Question 17

radiotherapy side effects

Answer 17

damage to marrow and intestinal mucosa
-inc suscept to infection by destroy radiosensitive lymphs
-may induce secondary tumor formation from DNA muts

Question 18

immunotherapy advantages

Answer 18

1. specifically tailor a resp to the tumor
2. fewer side effects that nonspecific therapy
3. more effective vs metastasis
4. tumor vaccines- inc immunogenicity or APCs, induce CTLs (melanoma)

Question 19

antibody therapies

Answer 19

1. Ab to surface immunoglobulin of B cell lymphomas
   -ADCC or complement required
   -problem w outgrowth of tumor cell mutants
2. Ab vs growth factor receptors
   -i.e. herceptin/trastuzumab target HER-2 receptor blocking
3. Ab coupled to toxin
   -i.e. bacterial, chemotherapeutic, radioisotopes must be endocytosed
4. bi specific
   -recog tumor Ag and immune system cells

Question 20

purging bone marrow tumor cells

Answer 20

via anti-tumor Ab + complement = tumor free source of bone marrow for autologous transplant in B cell lymphoma pts

Question 21

LAK cell therapy

adoptive cellular immunotherapy

Answer 21

lymphokine activated killer
-peripheral blood NK cultured in high dose IL-2
-reinfused into pt to kill tumor but most success with renal cell carcinoma and malig melanoma

Question 22

TIL theapy

adoptive cellulr immuno

Answer 22

tumor inflitrating lymphocytes
-leuks from solid tumors cultured with IL-2

Question 23

chimeric antigen receptors

CARs

Answer 23

genetically engineered receptors with
1. Ig variable genes for tumor antigen specific binding sites
2. cytoplasmic tails for signaling domains of antigen receptors and costim moles

Question 24

immune checkpoint therapy

Answer 24

-anti tumor lymphs dev high levels of CTLA-4 and PD-1 to inhibit anti tumor resp = immune checkpoint

use Ab to target CTLA-4 and PD1 to release T cell from checkpoint = vigorous anti tumor resp

inhibit the inhibitor