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IMMUNOLOGY > Lecture 21: Cancer Immunology > Flashcards

Lecture 21: Cancer Immunology Flashcards

1
Q

what cell types never enter G0 phase of cell cycle

A

skin & hair follicles
GI epithelium
bone marrow
male gametes

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2
Q

_______ regulate the normal progression of the cell cycle

A

Checkpoints

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3
Q

Cancer occurs when ______ accure in the DNA of cells. resulting in the progression of the cell cycle without regulation at checkpoints

A

Mutations

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4
Q

what are the 2 classes of genes in which mutations result in deregulation of the cell cycle

A

Tumor Suppressor Genes (the brakes)
(Proto) Oncogenes (accelerator)

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5
Q

what are tumor suppressor genes

A

genes that produce proteins that inhibit progression through the cell cycle

  • includes SNA repair enzymes and signaling proteins that block the cell cycle
  • most common causes of cancer
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6
Q

what type of mutations do tumor suppressor genes cause?

A

recessive mutations
- both copies of the gene have to be inactivated

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7
Q

what are (proto) oncogenes

A

genes that produce proteins that promote progression through the cell cycle

mutations cause constitutive activation of signaling proteins in growth pathways

driver mutation

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8
Q

what type of mutations do proto oncogenes cause

A

dominant
- only one copy of the gene has to be activated
- cancer viruses like FeLV cause these kinds of mutations

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9
Q

what are passenger mutations

A

mutations that don’t deregulate the cell cycle
- instead, they endow cancer cell w/ other physiological changes that give them growth advantages (ex: cells that can survive in hypoxic conditions)
- can be caused by continued exposure to carcinogens or radiation or arise spontaneously due to defective DNA repair enzymes

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10
Q

what are tumor antigens

A

DNA mutations in cancer cells produce proteins that the immune system might recognize as foreign

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11
Q

the accumulation of mutations progressively increases the _______ of cancer cells

A

Antigenicity

  • more mutations = more likely to be flagged by the immune system
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12
Q

what are tumor-specific antigens (TSA’s) or mutation-associated neoantigens (MANA’s)

A

unique to tumor cells
result from mutations in the exons of any gene or incorporation of oncogenic viruses

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13
Q

normal proteins that are inappropriately expressed by tumors

A

Tumor-associated antigens

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14
Q

what causes tumor associated antigens to form

A

mutations in gene regulatory elements

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15
Q

antigen that may be an overexpression of a protein or an expression of an embryonic or other immune privileged protein

A

tumor-associated antigen

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16
Q

explain immune surveillance

A

the capacity of the immune system to recognize and destroy transformed cells before they grow into tumors and to kill tumors after they are formed

  • involved innate and adaptive immune responses
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17
Q

how do antibodies promote tumor cell destruction?

A
  • enhancing innate immunity
  • serving as opsonins
  • activating complement and ADCC
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18
Q

cells capable of destroying tumor cells in a non-MHC restricted fasion. Are the first line of defense against many tumors

A

Natural Killer cells

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19
Q

cells that are effective against tumors with reduced levels of class I MHC

A

NK cells

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20
Q

what cells are strongly activated by INF-y and kill tumors by secreting TNF and ROS

A

Macrophages
- process and present tumor antigens to T cells

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21
Q

what is the most important immune mechanism for fighting tumors

A

tumor-specific Cytotoxic T-cells
- directed against tumor antigens presented by class I MHC molecules

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22
Q

what are the mechanisms for tumor elimination?

A
  1. tumor antigens get picked up by dendritic cells at the tumor site
  2. Cytotoxic T cells are activated in secondary lymphatics
  3. tumor-specific CTLs migrate back to the site and kill the tumor cells
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23
Q

what makes NK cells also critical in the killing of tumor cells

A

they recognize when MHC class I expression decreases…. which occurs in immunosuppressive tumor environments

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24
Q

what is ADCC

A

Antibody dependent cell-mediated cytotoxicity

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25
Q

immunoediting describes how ….

A

cancer cells respond to the immune system

26
Q

the killing of cancer cells by NKs and CTLs selects for cancer cells with…

A

Fewer MHC class I molecules
Fewer MANAs

27
Q

initial cancer cells are _______

A

immunogenic

28
Q

immune cell killing is a _____________ that results in the survival and growth of tumor cells with reduced ________

A

selective pressure
reduced immunogenicity

29
Q

most cancer cells have more ______ mutations than _____ mutations

A

more Passenger mutations than driver mutations

30
Q

Cancer cell-associated mechanisms of immune escape (4)

A
  • Decreased MHC expression (reduces recognition by CTLs)
  • Decreased expression of costimulatory molecules (causes CTL anergy and induces tolerance)
  • expression of T-cell inhibitory receptors
  • Normal immune attenuation
31
Q

what is the role of PD-L1 (ligand) in the expression of T cell inhibitory receptors

A

PD-L1 is a ligand for T cell receptor PD-1
- it increases CTL apoptosis
- decreases Treg apoptosis

32
Q

what is CTLA-4

A

homolog of CD28 that inhibits CTL function

33
Q

what cytokines do tumors secrete that activate repressive cell types

A

IL-4
IL-6
IL-10
TGF-B
MCF
PGE2
etc

34
Q

Myeloid-Derived Suppressor Cells (MDSCs) express _____ to inactivate CTLs

A

PD-L1

35
Q

what type of macrophages promote blood vessel formation and tissue repair

A

M2-polarized macrophages

36
Q

what cells secrete IL-10 and TGF-B, induces apoptosis of CD8 and CD4 T-cells, reduces available IL-2 by binding to CD25

A

Regulatory T cells

37
Q

what are myeloid derived suppressor cells

A

pre-myelocytes

38
Q

what is Piroxicam used for

A

treatment of transitional cell carcinoma in dogs

bladder cancer.think P for pee, bladder

39
Q

what kind of drug is Piroxicam

A

non specific cyclooxygenase (COX) inhibitor

40
Q

how does Piroxicam work

A

induced tumor cell apoptosis
- possibly by reducing angiogenesis

41
Q

what is Mycobacterial Cell Wall Fraction Immunomodulator used to treat

A

Dogs - Mixed Mammary tumors and mammary adenocarcinomas

Horses - sarcoids, equine respiratory disease, metritis caused by Streptococcus zooepidemicus

42
Q

what is the mechanism of Mycobacterial Cell Wall Fraction Immunomodulator?

A

local injection promotes inflammation
- oil in water emulsions of cell wall fractions
- indicated M1 macrophage activation and stimulates IL-1 release

43
Q

Glucocorticoid treatment for Lymphoma

A

prednisone/prednisolone
used as one of the drugs in the CHOP method

44
Q

how does prednisone work

A

induces apoptosis of most lymphocyte classes

45
Q

uses of prednisone

A

lymphoma & in non-CHOP protocols for treatment of multiple myeloma

46
Q

Guanine nucleotide analog treatment for lymphoma

A

Rabacfosadine (Tanovea CA-1)
- A pro drug that has to be metabolized into the active form
- active form gets incorporated in DNA chain of replicating cells

47
Q

How does Rabacfosadine work

A

doesn’t have a ribose base that DNA polymerase recognizes
terminates the replication of DNA chains during S phase of cell cycle

RabacfoSadine

48
Q

Drug used as part of the RESCUE protocol when remission of lymphoma in dogs can’t be achieved w/ CHOP

A

Asparaginase (Elspar)

49
Q

how does Asparaginase work

A
  • enzyme that degrades circulating asparagine
  • deprives lymphoid cancer of a necessary amino aicd
  • causes lethal metabolic stress
50
Q

What is Toceranic (Palladia)

A

a competitive antagonist of ATP binding to the kinase domain of c-kit

51
Q

what is c-kit

A

an oncogene mutated in 25-50% of all canine mast cell tumors

52
Q

how does mutant c-kit work

A
  • signals continuously in the absence of its ligand (constitutive activation)
  • causes unregulated cell proliferation of leukocytes, esp mast cells (driver mutation)
53
Q

what is the goal of anticancer vaccines?

A

they deliver antigens that induce an adaptive immune response and creation of memory T cells

54
Q

examples of specific anticancer vaccines

A

Feline Leukemia Virus
Canine melanoma (Oncept)
Canine B cell lymphoma
Marek’s Disease in Chickens

55
Q

_____ mutations occur in oncogenes or tumor suppressor genes and cause unregulated progression through the cell cycel

A

Driver

56
Q

_______ mutations may give cancer cells new activities but do not cause the disease

A

Passenger

57
Q

antigens that arise from mutations can be tumor _____ or tumor ______

A

tumor-specific or tumor-associated

58
Q

immunoediting selects for cells that are resistant to …

A

the immune system

59
Q

cancer treatments that alter immune system function in non-immune system cancers include…

A

Piroxicam and mycobacterial cell wall immunomodulatory

60
Q

cancer treatments for cancers of the immune system include…

A

prednisone
rabacfosadine
toceranib
asparaginase
vaccines

IMMUNOLOGY (26 decks)

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